Diisopropylethylamine → 5-{3-(cyanomethyl)-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]pyrazine-2-carboxamide
Reaction equation
Cl.[CH3:2][Si:3]([CH3:30])([CH3:29])[CH2:4][CH2:5][O:6][CH2:7][N:8]1[C:12]2=[N:13][CH:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][N:20]([C:22]4([CH2:26][C:27]#[N:28])[CH2:25][NH:24][CH2:23]4)[CH:21]=3)=[C:11]2[CH:10]=[CH:9]1.Cl[C:32]1[N:33]=[CH:34][C:35]([C:38]([NH:40][C@H:41]([CH:43]2[CH2:45][CH2:44]2)[CH3:42])=[O:39])=[N:36][CH:37]=1.C(N(CC)C(C)C)(C)C>>[C:27]([CH2:26][C:22]1([N:20]2[CH:21]=[C:17]([C:16]3[CH:15]=[CH:14][N:13]=[C:12]4[N:8]([CH2:7][O:6][CH2:5][CH2:4][Si:3]([CH3:29])([CH3:2])[CH3:30])[CH:9]=[CH:10][C:11]=34)[CH:18]=[N:19]2)[CH2:23][N:24]([C:32]2[N:33]=[CH:34][C:35]([C:38]([NH:40][C@H:41]([CH:43]3[CH2:45][CH2:44]3)[CH3:42])=[O:39])=[N:36][CH:37]=2)[CH2:25]1)#[N:28]Participants
4
Reactant 3
Product 1
Conditions
- Temperature
- 120 °C
Procedure
A mixture of {3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile HCl salt (200 mg, 0.4 mmol) (Example 40, Step 3), 5-chloro-N-[(1S)-1-cyclopropylethyl]pyrazine-2-carboxamide (100 mg, 0.46 mmol) in N,N-diisopropylethylamine (0.7 mL, 4 mmol) in a sealed vial was stirred at 120° C. for 1.5 h. After cooling it was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%) to afford the desired product (0.23 g).
Workup
- temperatureAfter cooling it
- concentrationwas concentrated under reduced pressure
- customThe residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%)
Sources & evidence
- ORD record
- ord-bd535b75c8b147ebb995a1575a5da358
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08691807B2
Reaction notes
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