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

HRID 1808898Notes

Reaction equation

HRID 1808898 reaction equation
[Cl:1][C:2]1[C:3]([N:24]2[CH2:29][CH2:28][N:27]([C:30]([C:32]3[C:33]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4[O:44][CH3:45])=[N:34][O:35][C:36]=3[CH3:37])=[O:31])[CH2:26][CH2:25]2)=[CH:4][C:5]([NH:12][C:13](=[O:23])[C:14]2[CH:19]=[CH:18][C:17]([N:20]([CH3:22])[CH3:21])=[CH:16][CH:15]=2)=[C:6]([CH:11]=1)[C:7](OC)=[O:8].[BH4-].[Na+]>CO.C1COCC1>[Cl:1][C:2]1[C:3]([N:24]2[CH2:25][CH2:26][N:27]([C:30]([C:32]3[C:33]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4[O:44][CH3:45])=[N:34][O:35][C:36]=3[CH3:37])=[O:31])[CH2:28][CH2:29]2)=[CH:4][C:5]([NH:12][C:13](=[O:23])[C:14]2[CH:15]=[CH:16][C:17]([N:20]([CH3:21])[CH3:22])=[CH:18][CH:19]=2)=[C:6]([CH2:7][OH:8])[CH:11]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 66692078Methyl 5-chloro-2-(4-(dimethylamino)benzamido)-4-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)benzoate

Product 1

HCID 66691603N-(4-Chloro-2-(hydroxymethyl)-5-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)phenyl)-4-(dimethylamino)benzamideYield 87.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of methyl 5-chloro-2-(4-(dimethylamino)benzamido)-4-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)benzoate (108 mg, 0.171 mmol) in MeOH (1 mL) and THF (3 mL) at room temperature was added sodium borohydride (32.3 mg, 0.854 mmol). The resulting reaction mixture was stirred at 40° C. for 2 hours. The product was purified by preparative HPLC(CH3CN/H2O-10 nM ammonium acetate) to give 90 mg (81% yield) of N-(4-Chloro-2-(hydroxymethyl)-5-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)phenyl)-4-(dimethylamino)benzamide. 1H-NMR (CDCl3, 400 MHz): δ 9.39 (1H, s), 8.03 (1H, s), 7.84 (2H, d, J=8.8 Hz), 7.58 (1H, dd, J1=7.5 Hz, J2=1.8 Hz), 7.52-7.45 (1H, m), 7.14 (1H, s), 7.11-6.99 (2H, m), 6.74 (2H, d, J=9.0 Hz), 4.71 (2H, s), 3.82 (3H, s), 3.77 (2H, s), 3.23 (2H, s), 2.97 (2H, s), 3.07 (6H, s), 2.57 (3H, s), 2.46 (2H, s).

Workup

  1. customThe resulting reaction mixture
  2. customThe product was purified by preparative HPLC(CH3CN/H2O-10 nM ammonium acetate)

Sources & evidence

ORD record
ord-bd67a58a678a4963bd3346b99c2e41da
Source dataset
uspto-grants-2013_01
Patent number
US08362004B2

Reaction notes

Loading…