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

Reaction equation

HRID 51623 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-040fd0ec05eb45a0ae629de36d5f1a20
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Linked notes

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