Chlorotrimethylsilane → 2-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carbonyl]-4-methyl-4-morpholino-pent-2-enenitrile

HRID 1429744Notes

Reaction equation

HRID 1429744 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:25][CH:26]3[CH2:29][CH2:28][N:27]3[C:30](=[O:34])[CH2:31][C:32]#[N:33])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][C:12]=3[F:24])[C:3]=12.[CH3:35][C:36]([N:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)([CH3:39])[CH:37]=O.N1CCCC1.[Si](Cl)(C)(C)C>C(Cl)Cl>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:25][CH:26]3[CH2:29][CH2:28][N:27]3[C:30]([C:31](=[CH:35][C:36]([CH3:39])([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[CH3:37])[C:32]#[N:33])=[O:34])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:13][C:12]=3[F:24])[C:3]=12

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 31268PyrrolidineHCID 27639872-Methyl-2-(morpholin-4-yl)propanalHCID 900011903-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidin-1-yl]-3-oxo-propanenitrile

Product 1

HCID 1237088622-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carbonyl]-4-methyl-4-morpholino-pent-2-enenitrileYield 19.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the mixture of 3-[2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidin-1-yl]-3-oxo-propanenitrile (90.6 mg, 0.200 mmol), 2-methyl-2-morpholino-propanal (98.3 mg, 0.590 mmol) in DCM (2 mL) in an ice bath was added pyrrolidine (0.1 mL, 1.19 mmol) and TMS-Cl (0.1 mL, 0.79 mmol). The ice bath was removed and the reaction mixture was stirred at room temperature for 1 hour and the reaction mixture directly loaded on silica gel plate, purified by EtOH:CH2Cl2 5% to get pure product 2-[2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carbonyl]-4-methyl-4-morpholino-pent-2-enenitrile (23 mg) as a white powder. LC-MS (ES, m/z): 597 [M+H]

Workup

  1. customThe ice bath was removed
  2. custompurified by EtOH

Sources & evidence

ORD record
ord-fdba50434b654ec499760dea65d2a7d6
Source dataset
uspto-grants-2015_01
Patent number
US08940744B2

Reaction notes

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