4-[(1RS,5RS,7SR)-5-Methyl-2,4-dioxo-3,6-diaza­bicyclo­[3.2.1]octan-7-yl]benzonitrile

Abstract

In the title compound, C₁₄H₁₃N₃O₂, the relative stereochemistry of the three stereogenic C atoms has been determined. In the crystal, N—H⋯O hydrogen bonds link the mol­ecules into chains of inversion dimers running along the b axis.

Related literature  

For general background to chemistry affording a bridged 3,6-diaza­bicyclo­[3.2.1]octane scaffold, substituted at the 3, 5, 6, and 7 positions, and the biological activity of this class of compounds, see: Kudryavtsev (2010 ▶).

Experimental  

Crystal data  

• C₁₄H₁₃N₃O₂

• M _r = 255.27

• Monoclinic,

• a = 14.8572 (13) Å

• b = 6.2269 (6) Å

• c = 13.1215 (12) Å

• β = 95.568 (1)°

• V = 1208.20 (19) ų

• Z = 4

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 150 K

• 0.40 × 0.15 × 0.10 mm

Data collection  

• Bruker SMART APEXII diffractometer

• Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.962, T _max = 0.990

• 11909 measured reflections

• 2924 independent reflections

• 2601 reflections with I > 2σ(I)

• R _int = 0.019

Refinement  

• R[F ² > 2σ(F ²)] = 0.040

• wR(F ²) = 0.110

• S = 1.06

• 2924 reflections

• 224 parameters

• All H-atom parameters refined

• Δρ_max = 0.35 e Å⁻³

• Δρ_min = −0.21 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supplementary Material

Supplementary material file. DOI: 10.1107/S1600536812020156/ff2066Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O2i	0.899 (18)	2.368 (19)	3.2377 (14)	162.8 (15)
N1—H1⋯O1ii	0.877 (17)	2.032 (17)	2.9019 (14)	171.3 (15)

Symmetry codes: (i) ; (ii) .

supplementary crystallographic information

Comment

In the title compound, 4-cyanophenyl substituent occupies endo position (Fig. 1). The –C(=O)NHC(=O)- system is planar within 0.046 (3) Å. The adjacent molecules are combined into double centrosymmetric chains along b-axis by N—H···O=C hydrogen bonds (Fig. 2). These chains are linked by weak van der Waals interactions.

3,6-Diazabicyclo[3.2.1]octanes are of interest as a structural motif for enzymes inhibitors. Synthesis of substituted 3,6-diazabicyclo[3.2.1]octane is based on copper(I) catalyzed intramolecular imide formation (Kudryavtsev (2010), Fig. 3).

Experimental

(2SR,4SR,5RS)-Methyl 4-carbamoyl-5-(4-cyanophenyl)-2-methylpyrrolidine-2-carboxylate (0.862 g, 3.0 mmol) was dissolved in 30 ml of DMF, 0.054 g (0.6 mmol) of CuCN were added, and the mixture was stirred under argon at 413 K during 6 h. The solvent was distilled off under reduced pressure, and the residue was dissolved in 20 ml of AcOEt, washed with saturated solution of NaHCO₃ (2 x 7 ml). Organic phase was dried under Na₂SO₄, concentrated and recrystallized from hexane–ethyl acetate. 4-((1RS,5RS,7SR- 5-methyl-2,4-dioxo-3,6-diazabicyclo[3.2.1]octan-7-yl)benzonitrile. Yield 0.490 g (64%), colourless crystals, m.p. 497–499 K. ¹H NMR (400 MHz, DMSO-d₆): δ 1.38 (s, 3H, CH₃), 2.00 (dd, J 11.8, 4.0, 1H, H-8a), 2.31 (d, J 11.8, 1H, H-8 b), 3.37 (br.s, 1H, H-1), 3.59 (d, J 7.8, 1H, N(6)H), 4.93 (dd, J 7.8, 5.8, 1H, H-7), 7.55 (d, J 8.3, 2H, Ar), 7.73 (d, J 8.3, 2H, Ar), 10.42(s, 1H, N(3)H). ¹³C NMR (100 MHz, DMSO-d₆): δ 18.73, 40.82, 52.78, 62.73, 63.09, 109.99, 119.42, 128.01 (2 C), 132.33 (2 C), 147.52, 174.04, 176.39. Anal. Calcd. for C₁₄H₁₃N₃O₂: C, 65.87; H, 5.13; N, 16.46. Found: C, 65.92; H, 5.17; N,16.63. The crystals were obtained by slow evaporation of saturated solution in hexane–ethyl acetate (2:3) mixture at ambient temperature.

Refinement

All hydrogen atoms were located in a difference Fourier map and refined with isotropic thermal parameters.

Figures

Fig. 1.

The molecular structure of the title compound, showing the numbering scheme adopted. Displacement ellipsoids are shown at the 50% probability level.

Fig. 2.

Hydrogen-bonded chains along b-axis in the structure of the title compound. H-bonds are shown as dashed lines.

Fig. 3.

Synthetic scheme.

Crystal data

C14H13N3O2	F(000) = 536
Mr = 255.27	Dx = 1.403 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5466 reflections
a = 14.8572 (13) Å	θ = 2.3–31.0°
b = 6.2269 (6) Å	µ = 0.10 mm−1
c = 13.1215 (12) Å	T = 150 K
β = 95.568 (1)°	Block, colourless
V = 1208.20 (19) Å3	0.40 × 0.15 × 0.10 mm
Z = 4

Data collection

Bruker SMART APEXII diffractometer	2924 independent reflections
Radiation source: fine-focus sealed tube	2601 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.019
ω scans	θmax = 28.0°, θmin = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −19→19
Tmin = 0.962, Tmax = 0.990	k = −8→8
11909 measured reflections	l = −17→17

Refinement

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040	Hydrogen site location: difference Fourier map
wR(F2) = 0.110	All H-atom parameters refined
S = 1.06	w = 1/[σ2(Fo2) + (0.0568P)2 + 0.4568P] where P = (Fo2 + 2Fc2)/3
2924 reflections	(Δ/σ)max < 0.001
224 parameters	Δρmax = 0.35 e Å−3
0 restraints	Δρmin = −0.21 e Å−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.01850 (6)	0.66158 (14)	0.61099 (7)	0.0262 (2)
O2	0.17560 (6)	0.06107 (15)	0.54975 (7)	0.0271 (2)
N1	0.10075 (7)	0.36899 (17)	0.57715 (8)	0.0213 (2)
N2	0.23232 (7)	0.66162 (17)	0.70043 (8)	0.0218 (2)
N3	0.47535 (9)	0.5189 (2)	0.21483 (9)	0.0350 (3)
C1	0.08167 (7)	0.54263 (19)	0.63735 (9)	0.0205 (2)
C2	0.16886 (8)	0.22065 (19)	0.60194 (9)	0.0203 (2)
C3	0.23153 (8)	0.27578 (19)	0.69563 (9)	0.0208 (2)
C4	0.28953 (8)	0.47800 (19)	0.67574 (8)	0.0202 (2)
C5	0.14651 (8)	0.5781 (2)	0.73407 (9)	0.0218 (2)
C6	0.17531 (8)	0.3600 (2)	0.77908 (9)	0.0237 (3)
C7	0.10602 (9)	0.7300 (2)	0.80748 (11)	0.0302 (3)
C8	0.44462 (9)	0.5099 (2)	0.29149 (9)	0.0262 (3)
C10	0.32690 (7)	0.48798 (19)	0.57236 (8)	0.0193 (2)
C11	0.32273 (10)	0.6744 (2)	0.51302 (11)	0.0326 (3)
C12	0.36129 (10)	0.6806 (2)	0.42077 (11)	0.0340 (3)
C13	0.40462 (8)	0.5001 (2)	0.38726 (9)	0.0227 (3)
C14	0.41036 (9)	0.3136 (2)	0.44601 (10)	0.0257 (3)
C15	0.37150 (9)	0.3091 (2)	0.53770 (10)	0.0251 (3)
H4	0.3428 (10)	0.470 (2)	0.7280 (12)	0.023 (4)*
H62	0.2141 (10)	0.378 (3)	0.8439 (12)	0.027 (4)*
H3	0.2689 (11)	0.147 (3)	0.7158 (12)	0.029 (4)*
H1	0.0636 (11)	0.346 (3)	0.5222 (13)	0.027 (4)*
H61	0.1244 (10)	0.265 (2)	0.7877 (11)	0.021 (3)*
H14	0.4399 (11)	0.192 (3)	0.4254 (13)	0.031 (4)*
H73	0.0524 (12)	0.658 (3)	0.8305 (14)	0.039 (5)*
H15	0.3758 (12)	0.181 (3)	0.5765 (13)	0.038 (4)*
H2	0.2219 (11)	0.755 (3)	0.6484 (14)	0.035 (4)*
H72	0.0885 (11)	0.867 (3)	0.7734 (13)	0.035 (4)*
H71	0.1509 (12)	0.751 (3)	0.8687 (15)	0.042 (5)*
H12	0.3569 (14)	0.814 (3)	0.3768 (16)	0.055 (6)*
H11	0.2931 (13)	0.803 (3)	0.5349 (14)	0.043 (5)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0212 (4)	0.0265 (5)	0.0309 (5)	0.0070 (3)	0.0025 (3)	−0.0009 (4)
O2	0.0292 (5)	0.0226 (4)	0.0297 (5)	0.0053 (4)	0.0045 (4)	−0.0035 (4)
N1	0.0191 (5)	0.0226 (5)	0.0221 (5)	0.0035 (4)	0.0016 (4)	−0.0014 (4)
N2	0.0200 (5)	0.0243 (5)	0.0219 (5)	0.0024 (4)	0.0064 (4)	−0.0021 (4)
N3	0.0419 (7)	0.0385 (7)	0.0266 (6)	−0.0124 (5)	0.0137 (5)	−0.0029 (5)
C1	0.0175 (5)	0.0220 (5)	0.0231 (5)	0.0011 (4)	0.0072 (4)	0.0012 (4)
C2	0.0198 (5)	0.0200 (5)	0.0219 (5)	0.0018 (4)	0.0070 (4)	0.0037 (4)
C3	0.0198 (5)	0.0238 (6)	0.0193 (5)	0.0054 (4)	0.0049 (4)	0.0031 (4)
C4	0.0175 (5)	0.0259 (6)	0.0174 (5)	0.0035 (4)	0.0029 (4)	−0.0009 (4)
C5	0.0200 (5)	0.0262 (6)	0.0200 (5)	0.0033 (4)	0.0062 (4)	−0.0016 (4)
C6	0.0240 (6)	0.0293 (6)	0.0189 (5)	0.0042 (5)	0.0079 (4)	0.0026 (5)
C7	0.0281 (6)	0.0365 (7)	0.0275 (6)	0.0063 (6)	0.0101 (5)	−0.0071 (6)
C8	0.0272 (6)	0.0288 (6)	0.0234 (6)	−0.0068 (5)	0.0055 (5)	−0.0021 (5)
C10	0.0160 (5)	0.0249 (6)	0.0172 (5)	0.0012 (4)	0.0027 (4)	−0.0008 (4)
C11	0.0405 (7)	0.0283 (7)	0.0311 (7)	0.0127 (6)	0.0146 (6)	0.0055 (5)
C12	0.0424 (8)	0.0315 (7)	0.0301 (7)	0.0107 (6)	0.0130 (6)	0.0108 (6)
C13	0.0204 (5)	0.0297 (6)	0.0184 (5)	−0.0040 (5)	0.0041 (4)	−0.0008 (5)
C14	0.0283 (6)	0.0246 (6)	0.0256 (6)	0.0024 (5)	0.0103 (5)	−0.0021 (5)
C15	0.0296 (6)	0.0234 (6)	0.0238 (6)	0.0053 (5)	0.0093 (5)	0.0032 (5)

Geometric parameters (Å, º)

O1—C1	1.2190 (14)	C5—C6	1.5257 (17)
O2—C2	1.2164 (15)	C6—H62	0.986 (16)
N1—C1	1.3845 (15)	C6—H61	0.976 (15)
N1—C2	1.3853 (15)	C7—H73	0.986 (19)
N1—H1	0.877 (17)	C7—H72	0.988 (18)
N2—C4	1.4793 (15)	C7—H71	1.002 (19)
N2—C5	1.4831 (15)	C8—C13	1.4426 (16)
N2—H2	0.899 (18)	C10—C15	1.3944 (16)
N3—C8	1.1457 (17)	C10—C11	1.3960 (17)
C1—C5	1.5331 (16)	C11—C12	1.3890 (18)
C2—C3	1.5080 (16)	C11—H11	0.971 (19)
C3—C6	1.5327 (15)	C12—C13	1.3879 (19)
C3—C4	1.5620 (17)	C12—H12	1.01 (2)
C3—H3	0.998 (16)	C13—C14	1.3919 (18)
C4—C10	1.5161 (15)	C14—C15	1.3843 (17)
C4—H4	0.997 (15)	C14—H14	0.931 (17)
C5—C7	1.5155 (16)	C15—H15	0.944 (18)
C1—N1—C2	124.90 (10)	C5—C6—H62	110.7 (9)
C1—N1—H1	116.8 (11)	C3—C6—H62	109.9 (9)
C2—N1—H1	118.0 (11)	C5—C6—H61	113.2 (9)
C4—N2—C5	108.84 (9)	C3—C6—H61	110.9 (9)
C4—N2—H2	113.2 (11)	H62—C6—H61	111.2 (12)
C5—N2—H2	111.3 (11)	C5—C7—H73	107.1 (11)
O1—C1—N1	120.48 (11)	C5—C7—H72	110.8 (10)
O1—C1—C5	123.50 (11)	H73—C7—H72	110.3 (14)
N1—C1—C5	115.97 (10)	C5—C7—H71	108.5 (11)
O2—C2—N1	120.71 (11)	H73—C7—H71	107.9 (15)
O2—C2—C3	124.53 (11)	H72—C7—H71	112.1 (15)
N1—C2—C3	114.76 (10)	N3—C8—C13	179.09 (15)
C2—C3—C6	108.91 (9)	C15—C10—C11	118.62 (11)
C2—C3—C4	110.75 (9)	C15—C10—C4	119.08 (10)
C6—C3—C4	101.02 (9)	C11—C10—C4	122.20 (11)
C2—C3—H3	108.4 (9)	C12—C11—C10	120.64 (12)
C6—C3—H3	114.4 (9)	C12—C11—H11	118.1 (11)
C4—C3—H3	113.1 (9)	C10—C11—H11	121.3 (11)
N2—C4—C10	115.62 (10)	C13—C12—C11	119.78 (12)
N2—C4—C3	104.39 (9)	C13—C12—H12	119.5 (12)
C10—C4—C3	116.00 (9)	C11—C12—H12	120.7 (12)
N2—C4—H4	108.7 (9)	C12—C13—C14	120.37 (11)
C10—C4—H4	106.4 (9)	C12—C13—C8	119.00 (12)
C3—C4—H4	105.1 (9)	C14—C13—C8	120.62 (11)
N2—C5—C7	112.09 (11)	C15—C14—C13	119.33 (11)
N2—C5—C6	102.15 (9)	C15—C14—H14	119.0 (10)
C7—C5—C6	115.05 (10)	C13—C14—H14	121.7 (10)
N2—C5—C1	107.06 (9)	C14—C15—C10	121.25 (12)
C7—C5—C1	111.09 (10)	C14—C15—H15	118.2 (11)
C6—C5—C1	108.79 (10)	C10—C15—H15	120.5 (11)
C5—C6—C3	100.36 (9)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O2i	0.899 (18)	2.368 (19)	3.2377 (14)	162.8 (15)
N1—H1···O1ii	0.877 (17)	2.032 (17)	2.9019 (14)	171.3 (15)

Symmetry codes: (i) x, y+1, z; (ii) −x, −y+1, −z+1.