Sodium borohydride → HCID 59375056, compound

HRID 661927Notes

Reaction equation

HRID 661927 reaction equation
[C:1]([CH:4]1[CH2:16][CH2:15][C:14]2[C:13]3[C:8](=[C:9]([C:25]([NH2:27])=[O:26])[CH:10]=[CH:11][C:12]=3[C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])[NH:7][C:6]=2[CH2:5]1)(=[O:3])[CH3:2].[BH4-].[Na+]>CO.C(Cl)Cl>[F:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[C:12]1[CH:11]=[CH:10][C:9]([C:25]([NH2:27])=[O:26])=[C:8]2[C:13]=1[C:14]1[CH2:15][CH2:16][CH:4]([CH:1]([OH:3])[CH3:2])[CH2:5][C:6]=1[NH:7]2

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 59375159HCID 59375159, compound

Product 1

HCID 59375056HCID 59375056, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 2-acetyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (Example 27-1, 30 mg, 0.081 mmol) and sodium borohydride (6.2 mg, 0.163 mmol) in methanol (1 mL) was stirred at rt for 1 h. The mixture was diluted with DCM, washed with NaHCO3 (aq) and water, and dried and concentrated. The residue was purified by preparative HPLC to provide two diastereomers of 5-(2,6-difluorophenyl)-2-(1-hydroxyethyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide. Each one was partitioned between 1 M aqueous sodium hydroxide and DCM, followed by drying and concentration, to provide the separated racemic diastereomers of 5-(2,6-difluorophenyl)-2-(1-hydroxyethyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide. The more polar diastereomer (Example 28-1) was a white solid (10 mg, 33%). 1H NMR (400 MHz, chloroform-d) δ 1.26 (d, J=6.59 Hz, 3H) 1.30-1.43 (m, 1H) 1.78-1.89 (m, 1H) 1.97-2.05 (m, J=12.74 Hz, 1H) 2.14-2.22 (m, 1H) 2.24-2.35 (m, 1H) 2.57 (dd, J=16.04, 10.77 Hz, 1H) 2.81 (dd, J=16.48, 5.05 Hz, 1H) 3.70-3.79 (m, 1H) 6.96-7.04 (m, 3H) 7.32-7.41 (m, 2 H) 10.05 (s, 1H). Mass spectrum m/z 371.1 (M+H)+. The less polar diastereomer (Example 28-2) was a white solid (8 mg, 27%). 1H NMR (400 MHz, chloroform-d) δ 1.26 (d, J=6.15 Hz, 3H) 1.34-1.40 (m, 1H) 1.42-1.53 (m, 1H) 1.75-1.90 (m, 2H) 2.24-2.35 (m, 1H) 2.68 (dd, J=16.26, 10.11 Hz, 1H) 2.94 (dd, J=16.26, 5.27 Hz, 1H) 3.80 (s, 1H) 6.96-7.05 (m, 3H) 7.34-7.40 (m, 2H) 10.05 (s, 1H). Mass spectrum m/z 371.1 (M+H)+.

Workup

  1. washwashed with NaHCO3 (aq) and water
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ab516077263a4c569bb5fc9dc16dd00e
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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