Sodium borohydride → 1-{2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-ylamino]-5-methylphenyl)ethanol

HRID 47554Notes

Reaction equation

HRID 47554 reaction equation
[CH2:1]1[N:12]2[C:13]3[C:9]([C@@H:10]4[CH2:17][NH:16][CH2:15][CH2:14][C@@H:11]42)=[CH:8][C:7]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=2[C:26](=[O:28])[CH3:27])=[CH:6][C:5]=3[CH2:4][O:3][CH2:2]1.[BH4-].[Na+]>CO.C(OCC)(=O)C>[CH2:1]1[N:12]2[C:13]3[C:9]([C@@H:10]4[CH2:17][NH:16][CH2:15][CH2:14][C@@H:11]42)=[CH:8][C:7]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=2[CH:26]([OH:28])[CH3:27])=[CH:6][C:5]=3[CH2:4][O:3][CH2:2]1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 600718871-{2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-ylamino]-5-methylphenyl}ethanone

Product 1

HCID 600719021-{2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-ylamino]-5-methylphenyl)ethanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-{2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-ylamino]-5-methylphenyl}ethanone from EXAMPLE 116 (20 mg, 0.05 mmol) in 5 ml methanol at 0° C. was added sodium borohydride (5.5 mg, 0.15 mmol). The solution was stirred with warming to room temperature for 2 h. The reaction was diluted with ethyl acetate, washed with water and brine, dried (MgSO4) and concentrated. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and the product containing fractions were concentrated, free-based with aq ammonium hydroxide, extracted with chloroform, washed with brine, dried (K2CO3) and concentrated to afford the title compound of EXAMPLE 117 as a mixture of diastereomers at the alcohol center. LRMS (ES)+: 380.3 (M+H)+.

Workup

  1. washwashed with water and brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC (
  5. washC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and the product
  6. additioncontaining fractions
  7. concentrationwere concentrated, free-based with aq ammonium hydroxide
  8. extractionextracted with chloroform
  9. washwashed with brine
  10. dry with materialdried (K2CO3)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-3cce2899badc4b81a18376b321b0b9df
Source dataset
uspto-grants-2004_03
Patent number
US06699852B2

Reaction notes

Loading…