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

HRID 1798747Notes

Reaction equation

HRID 1798747 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:14][C:15]([F:18])([F:17])[F:16].[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(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[NH2:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]2[N:26]([CH2:34][C:35]([N:11]3[CH2:12][CH2:13][N:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:14][C:15]([F:18])([F:16])[F:17])[CH:4]=4)[CH2:9][CH2:10]3)=[O:36])[N:27]=[C:28]([C:29]3[NH:33][CH:32]=[CH:31][N:30]=3)[C:21]=12

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592426861-(4-Chloro-3-trifluoromethoxyphenyl)piperazineHCID 1360797542-(4-amino-3-(1H-imidazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)acetic acid

Product 1

HCID 1359384912-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-3-trifluoromethoxyphenyl)piperazin-1-yl]ethanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-(4-chloro-3-trifluoromethoxyphenyl)piperazine didydrochloride salt (70 mg, 0.198 mmol, 1 equiv), [4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]acetic acid (96 mg, 1 equiv), HATU (98 mg, 1.3 equiv) and N,N-diisopropylethylamine (0.276 mL, 8 equiv) in DMF (0.5 mL) was stirred at room temperature for 3 h. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate, and purified by TLC to give 2-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-3-trifluoromethoxyphenyl)piperazin-1-yl]ethanone. 1H NMR (400 MHz, CD3OD) δ 8.18 (s, 1H), 7.39 (s, 1H,), 7.18 (d, 2H, J=8.8 Hz), 6.95 (s, 2H), 5.40 (s, 2H), 3.85 (m, 4H), 3.25 (m, 4H). The three remaining protons (from the amino group and the imidazole ring) were not observed due to the use of CD3OD as solvent. MS (ES) m/z 522.1 (M+H+).

Workup

  1. washwashed with saturated aqueous sodium bicarbonate
  2. dry with materialdried over sodium sulfate
  3. custompurified by TLC

Sources & evidence

ORD record
ord-5203e621f4c74cd0a0a0e3fce4fd32f1
Source dataset
uspto-grants-2013_01
Patent number
US08343975B2

Reaction notes

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