Sodium borohydride → (S)-5-(2,4-difluorophenoxy)-N-(4-(dimethylamino)-1-hydroxybutan-2-yl)-1-isobutyl-1H-indazole-6-carboxamide

HRID 909201Notes

Reaction equation

[F:1][C:2]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14]([NH:16][C@@H:17]([CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])[C:18](OC)=[O:19])=[O:15])[N:10]([CH2:27][CH:28]([CH3:30])[CH3:29])[N:9]=[CH:8]2.[BH4-].[Na+]>C1COCC1.CCO>[F:1][C:2]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14]([NH:16][C@@H:17]([CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])[CH2:18][OH:19])=[O:15])[N:10]([CH2:27][CH:28]([CH3:29])[CH3:30])[N:9]=[CH:8]2

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of (S)-methyl 2-(5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxamido)-4-(dimethylamino)butanoate (30d; Example 120, Steps A-E) (0.370 g, 0.76 mmol) and NaBH4 (0.114 g, 3.04 mmol) in THF/EtOH (20 mL, 3:2) was heated to 60° C. for 7 hours. The reaction mixture was concentrated under reduced pressure and diluted with dichloromethane. The slurry was chromatographed on Biotage eluting with 10% MeOH in dichloromethane with 1% triethylamine. The product was obtained as 0.337 g of viscous oil (97% yield). MS (ESI+) m/z 461 (M+1) detected; 1H NMR (400 mHz, CDCl3) δ 8.34 (d, 1H), 8.31 (s, 1H), 7.86 (s, 1H), 7.13 (m, 1H), 7.02 (s, 1H), 7.00 (m, 1H), 6.90 (m, 1H), 4.33 (m, 1H), 4.22 (d, 2H), 3.64 (m, 2H) 2.37 (m, 1H), 2.17 (s, 6H), 2.10 (m, 1H), 1.82 (m, 1H), 1.07 (m, 2H), 0.93 (d, 6H).

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
additiondiluted with dichloromethane
customThe slurry was chromatographed on Biotage
washeluting with 10% MeOH in dichloromethane with 1% triethylamine

Sources & evidence

ORD record: ord-1bc252c0861f438d9148be7a3affeda8
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08017641B2

Reaction notes

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