N-(4-Chloro-2-(hydroxymethyl)-5-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)phenyl)-4-(dimethylamino)benzamide → N-(4-chloro-2-formyl-5-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)phenyl)-4-(dimethylamino)benzamide

HRID 1808899Notes

Reaction equation

HRID 1808899 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([C:16]3[C:17]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[N:18][O:19][C:20]=3[CH3:21])=[O:15])[CH2:10][CH2:9]2)=[CH:6][C:5]([NH:30][C:31](=[O:41])[C:32]2[CH:37]=[CH:36][C:35]([N:38]([CH3:40])[CH3:39])=[CH:34][CH:33]=2)=[C:4]([CH2:42][OH:43])[CH:3]=1.C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>C(Cl)Cl>[Cl:1][C:2]1[C:7]([N:8]2[CH2:9][CH2:10][N:11]([C:14]([C:16]3[C:17]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[N:18][O:19][C:20]=3[CH3:21])=[O:15])[CH2:12][CH2:13]2)=[CH:6][C:5]([NH:30][C:31](=[O:41])[C:32]2[CH:33]=[CH:34][C:35]([N:38]([CH3:39])[CH3:40])=[CH:36][CH:37]=2)=[C:4]([CH:42]=[O:43])[CH:3]=1

Participants

4

Reactant 2

HCID 66691603N-(4-Chloro-2-(hydroxymethyl)-5-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)phenyl)-4-(dimethylamino)benzamideHCID 178418287HCID 178418287, compound

Product 1

HCID 86670897N-(4-chloro-2-formyl-5-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)phenyl)-4-(dimethylamino)benzamideYield 18.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-(4-chloro-2-(hydroxymethyl)-5-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)phenyl)-4-(dimethylamino)benzamide (60 mg, 0.099 mmol) in DCM (1.2 mL) was added to PCC (300 mg, 0.278 mmol) in an 8-mL vial. The reaction mixture was stirred at RT for 40 min. PCC on basic alumina was removed by filtration. The crude product was purified by flash chromatography (EtOAc/DCM, 20% gradient to 40%, Rf 0.66) to give 11.0 mg of the title compound. 1H-NMR (CDCl3, 400 MHz): δ 12.00 (1H, s), 9.77 (1H, s), 8.58 (1H, s), 7.97 (2H, d, J=9.0 Hz), 7.61-7.56 (2H, m), 7.52-7.45 (1H, m), 7.15-6.99 (2H, m), 6.77 (2H, d, J=9.0 Hz), 3.83 (3H, s), 3.80 (2H, s), 3.26 (2H, s), 3.17 (2H, s), 3.09 (6H, s), 2.59 (3H, s). HPLC/MS (Method H): (ES+) m/z (M+H)+=602; Rt=2.07 min.

Workup

  1. customPCC on basic alumina was removed by filtration
  2. customThe crude product was purified by flash chromatography (EtOAc/DCM, 20% gradient to 40%, Rf 0.66)

Sources & evidence

ORD record
ord-4e78f0b40cce40048a881dcfbc8c216a
Source dataset
uspto-grants-2013_01
Patent number
US08362004B2

Reaction notes

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