Cyanoacetic acid → 3-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidin-1-yl]-3-oxo-propanenitrile

HRID 1429743Notes

Reaction equation

HRID 1429743 reaction equation
[NH:1]1[CH2:4][CH2:3][CH:2]1[CH2:5][N:6]1[C:10]2=[N:11][CH:12]=[N:13][C:14]([NH2:15])=[C:9]2[C:8]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:18][C:17]=2[F:29])=[N:7]1.[C:30]([CH2:32][C:33](O)=[O:34])#[N:31].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C(Cl)Cl>[NH2:15][C:14]1[N:13]=[CH:12][N:11]=[C:10]2[N:6]([CH2:5][CH:2]3[CH2:3][CH2:4][N:1]3[C:33](=[O:34])[CH2:32][C:30]#[N:31])[N:7]=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)=[CH:18][C:17]=3[F:29])[C:9]=12

Participants

5

Reactant 3

HCID 9740Cyanoacetic acidHCID 111923Propylphosphonic anhydrideHCID 900012121-(Azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 900011903-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidin-1-yl]-3-oxo-propanenitrileYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-(azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine (236.4 mg, 0.610 mmol), 2-cyanoacetic acid (77.2 mg, 0.910 mmol) in DCM (8 mL) in ice bath, was added T3P (0.36 mL, 1.21 mmol) and TEA (0.34 mL, 2.42 mmol). The ice bath was removed and the reaction mixture was stirred at room temperature overnight. The reaction mixture was loaded onto the silica gel column, purified with 0-3% gradient MeOH:CH2CL2, to get 3-[2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidin-1-yl]-3-oxo-propanenitrile (201 mg) as yellow oil.

Workup

  1. customThe ice bath was removed
  2. custompurified with 0-3% gradient MeOH

Sources & evidence

ORD record
ord-bf23303e7274403794eae98ddc75708a
Source dataset
uspto-grants-2015_01
Patent number
US08940744B2

Reaction notes

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