Sodium borohydride → 4-(5-((4-fluorophenyl)(hydroxy)methyl)naphthalen-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

HRID 1811093Notes

Reaction equation

HRID 1811093 reaction equation
[F:1][C:2]1[CH:44]=[CH:43][C:5]([C:6]([C:8]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:9]=2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]2[C:30]3[C:29]4[C:24](=[CH:25][C:26]([C:31]([N:33]5[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]5)=[O:32])=[CH:27][CH:28]=4)[NH:23][C:22]=3[C:21]([C:40]([NH2:42])=[O:41])=[CH:20][CH:19]=2)=[O:7])=[CH:4][CH:3]=1.[BH4-].[Na+]>C(O)C.Cl>[F:1][C:2]1[CH:44]=[CH:43][C:5]([CH:6]([OH:7])[C:8]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:9]=2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]2[C:30]3[C:29]4[C:24](=[CH:25][C:26]([C:31]([N:33]5[CH2:34][CH2:35][N:36]([CH3:39])[CH2:37][CH2:38]5)=[O:32])=[CH:27][CH:28]=4)[NH:23][C:22]=3[C:21]([C:40]([NH2:42])=[O:41])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 666067924-(5-(4-fluorobenzoyl)naphthalen-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

Product 1

HCID 593750724-(5-((4-fluorophenyl)(hydroxy)methyl)naphthalen-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Procedure

A solution of 4-(5-(4-fluorobenzoyl)naphthalen-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide (Example 3-96, 30 mg, 0.051 mmol) in ethanol (0.5 mL) was treated with a couple granules of sodium borohydride and stirred at rt. After 90 min, the mixture was treated with 2 drops of 1 M hydrochloric acid and purified by preparative HPLC to provide two diastereomers of 4-(5-((4-fluorophenyl)(hydroxy)methyl)naphthalen-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide. Diastereomer 1 (Example 13-1) was isolated as a white powder (10.4 mg, 31%). 1H NMR (400 MHz, methanol-d4) δ 8.23 (1H, d, J=8.6 Hz), 7.99 (1H, d, J=7.7 Hz), 7.48-7.61 (3H, m), 7.36-7.46 (3H, m), 7.31 (1H, d, J=8.4 Hz), 7.19 (1H, dd, J=8.4, 7.0 Hz), 7.12 (1H, d, J=7.7 Hz), 7.02 (2H, t, J=8.8 Hz), 6.59 (1H, dd, J=8.1, 1.5 Hz), 6.51 (1H, s), 6.31 (1H, d, J=8.1 Hz), 3.68 (2H, br. s.), 3.35 (2H, br. s.), 2.43 (2H, br. s.), 2.28 (2H, br. s.), 2.23 (3H, s). Mass spectrum m/z 587.4 (M+H)+. Diastereomer 2 (Example 13-2) was isolated as a white powder (8 mg, 23%). 1H NMR (400 MHz, methanol-d4) δ 8.19 (1H, d, J=8.6 Hz), 7.99 (1H, d, J=7.9 Hz), 7.61 (1H, d, J=6.8 Hz), 7.59 (1H, s), 7.49-7.56 (1H, m), 7.43 (1H, dd, J=6.8, 0.7 Hz), 7.38 (2H, dd, J=8.5, 5.4 Hz), 7.26-7.32 (1H, m), 7.16-7.24 (1H, m), 7.11 (1H, d, J=7.7 Hz), 7.00 (2H, t, J=8.8 Hz), 6.61 (1H, dd, J=8.1, 1.3 Hz), 6.58 (1H, s), 6.36 (1H, d, J=8.1 Hz), 3.68 (2H, br. s.), 3.35 (2H, br. s.), 2.43 (2H, br. s.), 2.28 (2H, br. s.), 2.22 (3H, s). Mass spectrum m/z 587.4 (M+H)+.

Workup

  1. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-8a60b9ef0597489b92d5028d27ed78dd
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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