Triethylamine → (2R)-2-((4-Amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)methyl)-beta-oxo-1-pyrrolidinepropanenitrile

HRID 1854907Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:15]1[C:23]2[C:18](=[N:19][CH:20]=[N:21][C:22]=2[NH2:24])[N:17]([CH2:25][C@H:26]2[CH2:30][CH2:29][CH2:28][NH:27]2)[N:16]=1.[C:31]([CH2:33][C:34](O)=[O:35])#[N:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>O.CN(C)C=O>[NH2:24][C:22]1[N:21]=[CH:20][N:19]=[C:18]2[N:17]([CH2:25][C@H:26]3[CH2:30][CH2:29][CH2:28][N:27]3[C:34](=[O:35])[CH2:33][C:31]#[N:32])[N:16]=[C:15]([C:3]3[CH:4]=[CH:5][C:6]([O:8][C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=4)=[CH:7][C:2]=3[F:1])[C:23]=12

Participants

Conditions

Temperature: 25 °C

Procedure

Into a 100 mL, round-bottom flask, was placed 3-(2-fluoro-4-phenoxyphenyl)-1-[(2R)-pyrrolidin-2-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (278 mg, 0.69 mmol, 1.00 equiv), 2-cyanoacetic acid (36.8 mg, 0.43 mmol, 0.80 equiv), HATU (210 mg, 0.55 mmol. 0.80 equiv), triethylamine (109 mg. 1.08 mmol, 2.00 equiv), and N,N-dimethylformamide (50 mL). The resulting solution was stirred for 3 h at 25° C., then diluted with 200 mL of water and extracted with ethyl acetate and the organic layers combined, dried and concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (50/1) to give 200 mg (62%) of 3-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidin-1-yl]-3-oxopropane-nitrile as a yellow solid.

Workup

extractionextracted with ethyl acetate
customdried
concentrationconcentrated under vacuum
washeluted with dichloromethane/methanol (50/1)

Sources & evidence

ORD record: ord-5dc33007f6a243b5b4614b168225dcea
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962831B2

Reaction notes

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