Pyrrolidine → (1-(5-(4-Methylpyridin-2-yl)pyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(pyrrolidin-1-yl)methanone
Reaction equation
CN(C(ON1N=NC2[CH:12]=[CH:13][CH:14]=[N:15][C:10]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.N1CCCC1.[CH3:39][C:40]1[CH:45]=[CH:44][N:43]=[C:42]([C:46]2[CH:47]=[N:48][C:49]([N:52]3[C:60]4[C:55](=[CH:56][CH:57]=[C:58]([C:61](O)=[O:62])[CH:59]=4)[C:54]([S:64][CH3:65])=[CH:53]3)=[N:50][CH:51]=2)[CH:41]=1>CN(C=O)C>[CH3:39][C:40]1[CH:45]=[CH:44][N:43]=[C:42]([C:46]2[CH:47]=[N:48][C:49]([N:52]3[C:60]4[C:55](=[CH:56][CH:57]=[C:58]([C:61]([N:15]5[CH2:14][CH2:13][CH2:12][CH2:10]5)=[O:62])[CH:59]=4)[C:54]([S:64][CH3:65])=[CH:53]3)=[N:50][CH:51]=2)[CH:41]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
HATU (0.36 g, 0.95 mmol), diisopropylethylamine (0.41 mL, 2.39 mmol) and pyrrolidine (0.079 mL, 0.96 mmol) were added at 0° C. to a solution of the carboxylic acid 269b) (0.3 g, 0.79 mmol) in DMF (2 mL) and the resulting mixture was stirred at room temperature for 16 h. The reaction mixture was then poured onto water and extracted with dichloromethane (3×20 mL). The combined organic layers were washed with saturated sodium hydrogen carbonate solution and brine, dried over sodium sulfate and evaporated. The remnant was purified by flash column chromatography [silica; dichloromethane with 1% methanol]. White solid. Yield: 0.33 g (97% of theory)
Workup
- additionThe reaction mixture was then poured onto water
- extractionextracted with dichloromethane (3×20 mL)
- washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution and brine
- dry with materialdried over sodium sulfate
- customevaporated
- customThe remnant was purified by flash column chromatography [silica; dichloromethane with 1% methanol]
Sources & evidence
- ORD record
- ord-8ecddcfda1fa41a5987e33ed93f9e2ef
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09315490B2
Reaction notes
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