Reaction equation
C(N(CC)C(C)C)(C)C.OC(C(F)(F)F)=O.[NH:17]1[C:21]2=[N:22][CH:23]=[CH:24][C:25]([C:26]3[CH:27]=[N:28][N:29]([C:31]4([CH2:35][C:36]#[N:37])[CH2:34][NH:33][CH2:32]4)[CH:30]=3)=[C:20]2[CH:19]=[CH:18]1.[F:38][C:39]1[CH:40]=[C:41]([CH:46]=[CH:47][C:48]=1F)[C:42]([O:44][CH3:45])=[O:43].C([O-])(O)=O.[Na+]>CN1CCCC1=O>[C:36]([CH2:35][C:31]1([N:29]2[CH:30]=[C:26]([C:25]3[CH:24]=[CH:23][N:22]=[C:21]4[NH:17][CH:18]=[CH:19][C:20]=34)[CH:27]=[N:28]2)[CH2:32][N:33]([C:48]2[CH:47]=[CH:46][C:41]([C:42]([O:44][CH3:45])=[O:43])=[CH:40][C:39]=2[F:38])[CH2:34]1)#[N:37]Participants
6
Conditions
- Temperature
- 130 °C
Procedure
N,N-Diisopropylethylamine (1.6 mL, 9.5 mmol) was added to {3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile TFA salt (2.4 mmol) and methyl 3,4-difluorobenzoate (0.41 g, 2.4 mmol) (Aldrich, Cat. #: 594717) in N-methylpyrrolidinone (NMP) (5.0 mL). The reaction mixture was stirred at 130° C. overnight. The reaction mixture was worked up with saturated aqueous NaHCO3, extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in dichloromethane (0-5%) to afford the desired product (0.34 g, 33%). LCMS (M+H)+: m/z=431.1.
Workup
- extractionextracted with ethyl acetate (3×20 mL)
- washThe combined organic layers were washed with brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by flash chromatography on a silica gel column with methanol in dichloromethane (0-5%)
Sources & evidence
- ORD record
- ord-78532a02207d41af9cd1f76d05dafc4e
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09023840B2
Linked notes
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