Table 1.
Synthesis of 2- and 3-substituted 8-amino imidazo[1,2-a]pyrazines from 20a–e and 21a–e
| Starting Material | Ar1 | Ar2 | Ar3NH2 | Conditions | Product (Yield) |
|---|---|---|---|---|---|
| 20a | H |  |
22 | tBu-XPhos (5 mol %) Pd(dba)2 (1 mol %) K2CO3 (1.2 equiv) tBuOH, reflux, 40 h | 1 (41%) |
| 20b | H |  |
22 | tBu-XPhos (5 mol %) Pd(dba)2 (1 mol %) K2CO3 (1.2 equiv) tBuOH, reflux, 40 h | 2 (26%) |
| 20c | H |  |
22 | tBu-XPhos (5 mol %) Pd(dba)2 (1 mol %) K2CO3 (1.2 equiv) tBuOH, reflux, 40 h | 3 (30%) |
| 20d | H |  |
22 | tBu-XPhos (5 mol %) Pd(dba)2 (1 mol %) K2CO3 (1.2 equiv) tBuOH, reflux, 40 h | 4 (67%) |
| 20a | H |  |
23 | tBu-XPhos (5 mol %) Pd(dba)2 (1 mol %) K2CO3 (1.2 equiv) tBuOH, reflux, 46 h | 5 (35%) |
| 20e | H |  |
23 | DavePhos (3 mol %), Pd2(dba)3 (1 mol %) NaOtBu (1.4 equiv) toluene, reflux, 24 h | 6 (30%) |
| 21a |  |
H | 22 | DavePhos (3 mol %), Pd2(dba)3 (1 mol %) NaOtBu (1.4 equiv) toluene, reflux, 24 h | 7 (93%) |
| 21a |  |
H | 22 | DavePhos (3 mol %), Pd2(dba)3 (1 mol %) NaOtBu (1.4 equiv) toluene, 160 °C (μW), 10 min | 7 (46%) |
| 24 |  |
H | 22 | NaH (2 equiv), DMF, 100 °C, 20 h | 7 (72%) |
| 21b |  |
H | 22 | tBu-XPhos (5 mol %) Pd(dba)2 (1 mol %) K2CO3 (1.2 equiv) tBuOH, reflux, 48 h | 8 (13%) |
| 21c |  |
H | 22 | tBu-XPhos (5 mol %) Pd(dba)2 (1 mol %) K2CO3 (1.2 equiv) tBuOH, reflux, 48 h | 9 (2%) |
| 21d |  |
H | 22 | Pd(dppf)2Cl2 (2 mol %), K2CO3 (1.2 equiv), tBuOH, reflux, 21 h | 10 (29%) |
| 21a |  |
H | 23 | DavePhos (3 mol %), Pd2(dba)3 (1 mol %) NaOtBu (1.4 equiv) toluene, reflux, 24 h | 11 (22%) |
| 21a |  |
H | 23 | DavePhos (3 mol %), Pd2(dba)3 (1 mol %) NaOtBu (1.4 equiv) toluene, 160 °C (μW), 10 min | 11 (47%) |
| 21e |  |
H | 23 | tBu-XPhos (5 mol %) Pd(dba)2 (1 mol %) K2CO3 (1.2 equiv) tBuOH, reflux, 48 h | 12 (8%) |
| 21b |  |
H | 23 | DavePhos (3 mol %), Pd2(dba)3 (1 mol %) NaOtBu (1.4 equiv) toluene, reflux, 24 h | 13 (9%) |