Triethylamine → (R)-(7-Chlorothieno[3,2-b]pyridin-2-yl)(3-(dimethylamino)pyrrolidin-1-yl)methanone
Reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[CH3:32][N:33]([CH3:39])[C@@H:34]1[CH2:38][CH2:37][NH:36][CH2:35]1.[Li+].[Cl:41][C:42]1[CH:47]=[CH:46][N:45]=[C:44]2[CH:48]=[C:49]([C:51]([O-])=[O:52])[S:50][C:43]=12>CN(C=O)C>[Cl:41][C:42]1[CH:47]=[CH:46][N:45]=[C:44]2[CH:48]=[C:49]([C:51]([N:36]3[CH2:37][CH2:38][C@@H:34]([N:33]([CH3:39])[CH3:32])[CH2:35]3)=[O:52])[S:50][C:43]=12Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
HATU (4.99 g, 26.25 mmol) and Et3N (7.23 mL, 52.50 mmol) was added to a solution of (3R)-N,N-dimethylpyrrolidin-3-amine (1.0 g, 17.5 mmol) and 7-chlorothieno[3,2-b]pyridine-2-carboxylic acid lithium salt (3.85 g, 17.5 mmol) in 30 mL DMF at 0° C. The reaction mixture was stirred at 0° C. for 15 min and solvent was concentrated. The residue was partition between H2O and 10% CH3OH in EtOAC. The organic layer was dried over MgSO4 and concentrated. The residue was purified by flash column chromatography (5-7% CH3OH in CH2Cl2) to give a white solid (1.74 g, 32%). 1H NMR (CD3OD) δ 8.57 (1H, d, J=5.2 Hz), 7.90 (1H, d, J=7.9 Hz), 7.48 (1H, d, J=5.2 Hz), 4.11-3.97 (1H, m), 3.90-3.36 (3H, m), 2.99-2.90 (1H, m), 2.30 (3H, s), 2.26 (3H, s), 1.97-1.72 (2H, m). ESIMS (MH+): 310.10.
Workup
- concentrationsolvent was concentrated
- customThe residue was partition between H2O and 10% CH3OH in EtOAC
- dry with materialThe organic layer was dried over MgSO4
- concentrationconcentrated
- customThe residue was purified by flash column chromatography (5-7% CH3OH in CH2Cl2)
Sources & evidence
- ORD record
- ord-07055d14514f443abbebef62e012cc40
- Source dataset
- uspto-grants-2004_12
- Patent number
- US06833456B2
Reaction notes
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