Potassium Carbonate → 2-((4-Amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-5-bromo-3-(2-chlorobenzyl)quinazolin-4(3H)-one

HRID 524556Notes

Reaction equation

HRID 524556 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:22])[N:5]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21])[C:6]([CH2:12]Cl)=[N:7]2.C(=O)([O-])[O-].[K+].[K+].[Si]([O:36][C:37]1[CH:38]=[C:39]([C:43]2[C:51]3[C:46](=[N:47][CH:48]=[N:49][C:50]=3[NH2:52])[NH:45][N:44]=2)[CH:40]=[CH:41][CH:42]=1)(C(C)(C)C)(C)C>CN(C=O)C>[NH2:52][C:50]1[N:49]=[CH:48][N:47]=[C:46]2[N:45]([CH2:12][C:6]3[N:5]([CH2:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[Cl:21])[C:4](=[O:22])[C:3]4[C:8](=[CH:9][CH:10]=[CH:11][C:2]=4[Br:1])[N:7]=3)[N:44]=[C:43]([C:39]3[CH:40]=[CH:41][CH:42]=[C:37]([OH:36])[CH:38]=3)[C:51]=12

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 665792385-bromo-3-(2-chlorobenzyl)-2-(chloromethyl)quinazolin-4(3H)-oneHCID 178455042HCID 178455042, compound

Product 1

HCID 569660532-((4-Amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-5-bromo-3-(2-chlorobenzyl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred mixture of 5-bromo-3-(2-chlorobenzyl)-2-(chloromethyl)quinazolin-4(3H)-one (2) (100 mg, 0.25 mmol) and potassium carbonate (42 mg, 0.30 mmol) in DMF (2.5 mL) was added a solution of 3-(3-(tert-Butyldimethylsilyloxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (6) (94 mg, 0.28 mmol) in DMF (2.5mL) and the reaction mixture was stirred at RT for 18 hr. Potassium carbonate (3×35 mg, 0.75 mmol) was added in three portions over 30 hr. after which the solvent was removed in vacuo and the crude material was purified by flash column chromatography, eluting with 4.5% methanol in DCM, to afford the title compound, Intermediate A, (94 mg, 64%) as a off-white solid: Rt 2.01 min; m/z 588/590 (M+H)+, (ES+).

Workup

  1. customafter which the solvent was removed in vacuo
  2. customthe crude material was purified by flash column chromatography
  3. washeluting with 4.5% methanol in DCM

Sources & evidence

ORD record
ord-e5eb253b35eb45c692ce93a7cd67de42
Source dataset
uspto-grants-2016_05
Patent number
US09340545B2

Reaction notes

Loading…