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Sodium Carbonate Monohydrate → N1-phenyl-2-(4-{4-chloro-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine-5-yl}phenyl)acetamide

HRID 51623
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HRID 51623 반응식
[Cl:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:25]1([NH:31][C:32](=[O:49])[CH2:33][C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:35]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[C:25]1([NH:31][C:32](=[O:49])[CH2:33][C:34]2[CH:39]=[CH:38][C:37]([C:10]3[C:3]4[C:2]([Cl:1])=[N:7][CH:6]=[N:5][C:4]=4[N:8]([CH:12]4[CH2:17][CH2:16][CH:15]([N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)[CH2:14][CH2:13]4)[CH:9]=3)=[CH:36][CH:35]=2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
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참가 물질

6

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HCID 2735133Sodium Carbonate MonohydrateHCID 22736360N1-phenyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamideHCID 178480945HCID 178480945, 화합물

생성물 1

HCID 22736191N1-phenyl-2-(4-{4-chloro-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine-5-yl}phenyl)acetamide수율 62.5%

시약·촉매·용매 2

HCID 962
Water
용매
HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A mixture of cis-4-chloro-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine (1.0 g, 2.18 mmol), N1-phenyl -2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamide (0.81 g, 2.40 mmol), tetrakis(triphenyl-phosphine)palladium (70 mg, 0.131 mmol) and sodium carbonate monohydrate (0.65 g, 2.40 mmol) in ethylene glycol dimethyl ether (16 mL) and water (8 mL) was heated at 85° C. under an atmosphere of nitrogen for 18 hours. The mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica using dichloromethane/methanol (9:1) as an eluent to give N1-phenyl-2-(4-{4-chloro-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine-5-yl}phenyl)acetamide (0.74 g, 62%): 1H NMR (DMSO-d6, 400 MHz) 10.20(s, 1H), 8.66(s, 1H), 7.81(s, 1H), 7.62(d, 2H), 7.52(d, 2H), 7.41(d, 2H), 7.31(t, 2H), 7.04(t, 1H), 4.83(m, 1H), 3.70(s, 2H)<2.05-2.5(m, 13H), 2.17(s, 3H), 1.59-1.77(m, 4H); RP-HPLC (Hypersil HS C18, 5 m, 100 A, 250×4.6 mm; 25%-100% acetontrile over 10 min, 1 mL/min) tr 8.23 min.; MS:MH+ 543.2.

후처리

  1. temperatureThe mixture was cooled to ambient temperature
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was purified by flash chromatography on silica

출처 및 근거

ORD 기록
ord-040fd0ec05eb45a0ae629de36d5f1a20
출처 데이터셋
uspto-grants-2004_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06713474B2

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