Diisopropylethylamine → 1-(2-((2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)methyl)-4,4-difluoropiperidin-1-yl)-3-methoxypropan-1-one
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH2:18][CH:19]4[CH2:24][C:23]([F:26])([F:25])[CH2:22][CH2:21][NH:20]4)[C:14]([F:27])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.ClC1C=C2C(C3N=C(NCC4CC(F)(F)CCN4C(OC(C)(C)C)=O)C(F)=CN=3)=CNC2=NC=1.CCN(C(C)C)C(C)C.[CH3:71][O:72][CH2:73][CH2:74][C:75](Cl)=[O:76]>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH2:18][CH:19]4[CH2:24][C:23]([F:26])([F:25])[CH2:22][CH2:21][N:20]4[C:75](=[O:76])[CH2:74][CH2:73][O:72][CH3:71])[C:14]([F:27])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1Participants
7
Reactant 4
HCID 81531Diisopropylethylamine
HCID 27597283-Methoxypropanoyl chloride
HCID 67285135tert-butyl 2-((2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)methyl)-4,4-difluoropiperidine-1-carboxylate
HCID 672899362-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-((4,4-difluoropiperidin-2-yl)methyl)-5-fluoropyrimidin-4-amineProduct 1
Reagents, catalysts & solvents 2
Procedure
To a solution of 2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-[(4,4-difluoro-2-piperidyl)methyl]-5-fluoro-pyrimidin-4-amine, 13k, (0.086 g, 0.198 mmol) in CH2Cl2 (1 mL), DMF (0.5 mL) and iPr2NEt (0.10 mL, 0.57 mmol) was added 3-methoxypropanoyl chloride (2.43 g, 0.20 mmol). The reaction mixture was stirred at room temperature for 17 hours. All volatiles were removed at reduced pressure and the residue was purified via silica gel chromatography to give a mixture enriched in desired product, 13, which was repurified via preparatory HPLC.
Workup
- customAll volatiles were removed at reduced pressure
- customthe residue was purified via silica gel chromatography
- customto give a mixture
Sources & evidence
- ORD record
- ord-c97c5d614a304a42942b9f83362c3632
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09345708B2
Reaction notes
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