Triethylamine → 3-[(2R)-2-([4-amino-3-[4-(3-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidin-1-yl]-3-oxopropanenitrile

HRID 409054Notes

Reaction equation

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

Participants

Conditions

Temperature: 25 °C

Procedure

Into a 100-mL round-bottom flask, was placed 3-[4-(3-fluorophenoxy)phenyl]-1-[(2R)-pyrrolidin-2-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (216 mg, 0.53 mmol, 1.00 equiv), 2-cyanoacetic acid (36.8 mg, 0.43 mmol, 0.80 equiv), HATU (166 mg, 0.44 mmol, 0.80 equiv), triethylamine (109 mg, 1.08 mmol, 2.00 equiv), N,N-dimethylformamide (50 mL). The resulting solution was stirred for 3 h at 25° C. The resulting solution was extracted with ethyl acetate and the organic layers combined and concentrated under vacuum. The residue was loaded on a silica gel column and eluted with dichloromethane methanol (50 1) to give 150 mg (60%) of 3-[(2R)-2-([4-amino-3-[4-(3-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidin-1-yl]-3-oxopropanenitrile as a yellow solid.

Workup

customInto a 100-mL round-bottom flask, was placed
extractionThe resulting solution was extracted with ethyl acetate
concentrationconcentrated under vacuum
washeluted with dichloromethane methanol (50 1)

Sources & evidence

ORD record: ord-788ebfa2c5504786a516746ab5e4578a
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759358B1

Reaction notes

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