Sodium Carbonate Monohydrate → N1-{4-[4-amino-1-(4-hydroxy-2-cyclopentenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-trifluoromethylbenzamide

HRID 2056048노트

반응식

HRID 2056048 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:16][CH:15]([OH:17])[CH:14]=[CH:13]3)[N:9]=[C:10](I)[C:3]=12.[CH3:18][O:19][C:20]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:22][C:21]=1[NH:35][C:36](=[O:48])[C:37]1[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][C:38]=1[F:47].O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:16][CH:15]([OH:17])[CH:14]=[CH:13]3)[N:9]=[C:10]([C:24]3[CH:23]=[CH:22][C:21]([NH:35][C:36](=[O:48])[C:37]4[CH:42]=[CH:41][C:40]([C:43]([F:45])([F:46])[F:44])=[CH:39][C:38]=4[F:47])=[C:20]([O:19][CH3:18])[CH:25]=3)[C:3]=12

참가 물질

6

반응물 3

HCID 2735133Sodium Carbonate MonohydrateHCID 223473184-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-cyclopenten-1-olHCID 22347319N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide

생성물 1

HCID 22347104N1-{4-[4-amino-1-(4-hydroxy-2-cyclopentenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-trifluoromethylbenzamide수율 97.1%

시약·촉매·용매 2

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

A mixture of 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-cyclopenten-1-ol (0.12 g, 0.35 mmol), N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-trifluoromethylbenzamide (0.23 g, 0.53 mmol), tetrakis(triphenyl-phosphine)palladium(0) (0.02 g, 0.02 mmol) and sodium carbonate monohydrate (0.11 g, 0.88 mmol) was heated in a mixture of ethylene glycol dimethyl ether (6 mL) and water (3 mL) at 85° C. for 6 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and solvents were removed under the reduced pressure. The residue was purified by preparative HPLC to yield N1-{4-[4-amino-1-(4-hydroxy-2-cyclopentenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-trifluoromethylbenzamide (0.18 g, 0.34 mmol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 9.89 (dd, 1H), 8.31(d, 1H), 8.26 (s, 1H), 8.00 (t, 1H), 7.88 (d, 1H), 7.75 (d, 1H), 7.32 (s, 1H), 7.29 (d, 1H), 6.90 (br, 2H), 6.09 (d, 1H), 5.93 (d, 1H), 5.76 (m, 1H), 5.31 (m, 1H), 4.74 (m, 1H), 3.94 (s, 3H), 2.84 (m, 1H), 2.02 (m, 1H); RP-HPLC (Hitachi HPLC, Hypersil C18, 5 μm, 100A, 250×4.6 mm; 25%-100% acetonitrile—0.05M ammonium acetate over 10 min, 1 mL/min) Rt 8.50 min. MS: MH+ 529.

후처리

  1. customsolvents were removed under the reduced pressure
  2. customThe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-2dab5ad88a4a485d91824d126354641c
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07332497B2

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