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 2056048ノート

反応式

HRID 2056048 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-2dab5ad88a4a485d91824d126354641c
出典データセット
uspto-grants-2008_02
特許番号
US07332497B2

反応ノート

読み込み中…