Sodium Carbonate Monohydrate → HCID 178476504, compound

HRID 432502Notes

Reaction equation

HRID 432502 reaction equation
[CH3:1][C:2]1[CH2:6][CH:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:4]([C:13]2[CH:18]=[CH:17][C:16](B3[O:23][C:22]([CH3:25])(C)C(C)(C)O3)=[CH:15][CH:14]=2)[N:3]=1.I[C:29]1[C:37]2[C:32](=[N:33][CH:34]=[N:35][C:36]=2[NH2:38])[N:31]([C@H:39]2[CH2:44][CH2:43][C@H:42]([N:45]3[CH2:50][CH2:49][N:48]([CH3:51])[CH2:47][CH2:46]3)[CH2:41][CH2:40]2)[N:30]=1.O.[C:53](=[O:56])([O-])[O-:54].[Na+].[Na+]>COCCOC.O>[C:22]([OH:54])(=[O:23])[CH3:25].[C:53]([OH:54])(=[O:56])[CH3:1].[CH3:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:4]([C:13]2[CH:14]=[CH:15][C:16]([C:29]3[C:37]4[C:32](=[N:33][CH:34]=[N:35][C:36]=4[NH2:38])[N:31]([C@H:39]4[CH2:40][CH2:41][C@H:42]([N:45]5[CH2:46][CH2:47][N:48]([CH3:51])[CH2:49][CH2:50]5)[CH2:43][CH2:44]4)[N:30]=3)=[CH:17][CH:18]=2)[N:3]=1

Participants

6

Reactant 3

HCID 2735133Sodium Carbonate MonohydrateHCID 22346960HCID 22346960, compoundHCID 178481015HCID 178481015, compound

Product 1

HCID 178476504HCID 178476504, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 3-methyl-5-phenyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4,5-dihydro-1H-pyrazole (0.102 g, 0.000283 mol), trans-3-iodo-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.104 g, 0.000236 mol), tetrakis-(triphenylphosphine)palladium (0.016 g, 0.000014 mol) and sodium carbonate monohydrate (0.073 g, 0.00055 mol) was heated in a mixture of ethylene glycol dimethyl ether (5 mL) and water (3 mL) at 80° C. for 16 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 (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile-0.1M ammonium acetate over 25 min, 21 mL/min) to yield trans-3-[4-(3-methyl-5-phenyl-1H-1-pyrazolyl)phenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine diacetate (0.094 g, 0.000141 mol) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 8.23 (s, 1H), 7.64 (d, 2H), 7.37 (m, 7H), 6.49 (s, 1H), 4.63 (m, 1H), 2.6-2.2 (br, 9H), 2.30 (s, 3H), 2.13 (s, 3H), 2.05 (m, 6H), 1.91 (s, 6H), 1.46 (m, 2H); RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 14.10 min. MS: MH+ 548.

Workup

  1. customsolvents were removed under the reduced pressure
  2. customThe residue was purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile-0.1M ammonium acetate over 25 min, 21 mL/min)

Sources & evidence

ORD record
ord-e5219de4cc02468a9a4b86a3dacc3a78
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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