Diisopropylethylamine → 2-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-2-fluoro-5-methoxyphenyl)-piperazin-1-yl]ethanone

HRID 1842853Notes

Reaction equation

HRID 1842853 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:9]([O:10][CH3:11])=[CH:8][C:7]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[C:6]([F:18])[CH:5]=1.[NH2:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]2[N:26]([CH2:34][C:35](O)=[O:36])[N:27]=[C:28]([C:29]3[NH:30][CH:31]=[CH:32][N:33]=3)[C:21]=12.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[NH2:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]2[N:26]([CH2:34][C:35]([N:15]3[CH2:14][CH2:13][N:12]([C:7]4[CH:8]=[C:9]([O:10][CH3:11])[C:4]([Cl:3])=[CH:5][C:6]=4[F:18])[CH2:17][CH2:16]3)=[O:36])[N:27]=[C:28]([C:29]3[NH:33][CH:32]=[CH:31][N:30]=3)[C:21]=12

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 671040051-(4-Chloro-2-fluoro-5-methoxyphenyl)piperazine dihydrochlorideHCID 1360797542-(4-amino-3-(1H-imidazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)acetic acid

Product 1

HCID 1359384902-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-2-fluoro-5-methoxyphenyl)-piperazin-1-yl]ethanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(4-chloro-2-fluoro-5-methoxyphenyl)-piperazine dihydrochloride salt (65.2 mg, 0.206 mmol, 1 equiv), [4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]acetic acid (50 mg, 1 equiv), BOP reagent (109 mg, 1.7 equiv) and N,N-diisopropylethylamine (0.165 mL, 5 equiv) in DMF (0.5 mL) was stirred at room temperature overnight. Reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent) purification gave 2-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-2-fluoro-5-methoxyphenyl)-piperazin-1-yl]ethanone. MS (ES) m/z 486.5 (M+H+).

Workup

  1. customReverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent) purification

Sources & evidence

ORD record
ord-3c918556b46d4131a457eeb18d08601d
Source dataset
uspto-grants-2015_02
Patent number
US08946240B2

Reaction notes

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