Sodium Carbonate Monohydrate → HCID 178476635, compound

HRID 432343Notes

Reaction equation

HRID 432343 reaction equation
[C:1]1([CH:7]2[CH2:11][C:10](=[O:12])[N:9]([C:13]3[CH:18]=[CH:17][C:16](B4[O:23][C:22]([CH3:25])(C)C(C)(C)O4)=[CH:15][CH:14]=3)[C:8]2=[O:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:30]1[C:38]2[C:33](=[N:34][CH:35]=[N:36][C:37]=2[NH2:39])[N:32]([C@H:40]2[CH2:45][CH2:44][C@@H:43]([N:46]3[CH2:51][CH2:50][N:49]([CH3:52])[CH2:48][CH2:47]3)[CH2:42][CH2:41]2)[N:31]=1.[OH2:53].[C:54](=[O:57])([O-])[O-:55].[Na+].[Na+]>COCCOC.O>[C:22]([OH:55])(=[O:23])[CH3:25].[NH2:39][C:37]1[N:36]=[CH:35][N:34]=[C:33]2[N:32]([C@H:40]3[CH2:45][CH2:44][C@@H:43]([N:46]4[CH2:51][CH2:50][N:49]([CH3:52])[CH2:48][CH2:47]4)[CH2:42][CH2:41]3)[N:31]=[C:30]([C:16]3[CH:15]=[CH:14][C:13]([NH:9][C:10](=[O:12])[CH2:11][CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[C:8]([OH:28])=[O:53])=[CH:18][CH:17]=3)[C:38]=12.[C:54]([OH:55])(=[O:57])[CH3:1].[NH2:39][C:37]1[N:36]=[CH:35][N:34]=[C:33]2[N:32]([C@H:40]3[CH2:45][CH2:44][C@@H:43]([N:46]4[CH2:51][CH2:50][N:49]([CH3:52])[CH2:48][CH2:47]4)[CH2:42][CH2:41]3)[N:31]=[C:30]([C:16]3[CH:15]=[CH:14][C:13]([NH:9][C:8](=[O:28])[CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:11][C:10]([OH:12])=[O:55])=[CH:18][CH:17]=3)[C:38]=12

Participants

7

Reactant 3

HCID 2735133Sodium Carbonate MonohydrateHCID 22346997HCID 22346997, compoundHCID 178481014HCID 178481014, compound

Product 2

HCID 178476635HCID 178476635, compoundHCID 178476636HCID 178476636, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 3-phenyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,5-pyrrolidinedione (0.35 g, 0.00093 mol), cis-3-iodo-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.34 g, 0.000773 mol), tetrakis-(triphenylphosphine)palladium (0.053 g, 0.000046 mol) and sodium carbonate monohydrate (0.24 g, 0.00193 mol) was heated in a mixture of ethylene glycol dimethyl ether (14 mL) and water (7 mL) at 80° C. for sixteen 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 cis-4-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}anilino)-4-oxo-2-phenylbutanoic acid acetate (0.150 g, 0.000233 mol) and cis-4-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}anilino)-4-oxo-3-phenylbutanoic acid acetate (0.11 g, 0.000171 mol) both as white solids.

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-0379f3dca08b4404899dd7c45dc19e87
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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