Ammonium formate → HCID 59375151, compound

HRID 662003Notes

Reaction equation

HRID 662003 reaction equation
[CH3:1][C:2]1[C:3](=[O:35])[N:4]([C:8]2[C:9]([CH3:34])=[C:10]([C:14]3[C:26]4[C:25]5[C:20](=[CH:21][C:22]([C:27]([OH:30])([CH3:29])[CH3:28])=[CH:23][CH:24]=5)[NH:19][C:18]=4[C:17]([C:31]([NH2:33])=[O:32])=[CH:16][CH:15]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:5][C:6]=1[CH3:7].C([O-])=O.[NH4+]>CO.[Pd].C(Cl)Cl>[CH3:1][CH:2]1[CH:6]([CH3:7])[CH2:5][N:4]([C:8]2[C:9]([CH3:34])=[C:10]([C:14]3[C:26]4[C:25]5[C:20](=[CH:21][C:22]([C:27]([OH:30])([CH3:29])[CH3:28])=[CH:23][CH:24]=5)[NH:19][C:18]=4[C:17]([C:31]([NH2:33])=[O:32])=[CH:16][CH:15]=3)[CH:11]=[CH:12][CH:13]=2)[C:3]1=[O:35]

Participants

6

Reactant 2

HCID 2723923Ammonium formate4×HCID 66606416HCID 66606416, compound

Product 1

HCID 59375151HCID 59375151, compoundYield 55%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(3-(3,4-dimethyl-2-oxo-2,5-dihydro-1H-pyrrol-1-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide (Example 81-21, 20 mg, 0.043 mmol) and ammonium formate (27.0 mg, 0.428 mmol) in methanol (5 mL) was treated with 10% palladium on charcoal (20 mg, 0.019 mmol). The mixture was stirred under nitrogen at rt for 2 h. Additional ammonium formate (27.0 mg, 0.428 mmol) was added and the mixture was stirred at rt overnight. More ammonium formate (57 mg) and 10% palladium on charcoal (40 mg) were added, and after 6 h more additional ammonium formate (57 mg) was added. The mixture was again stirred overnight, then was diluted with DCM and filtered through Celite. The filtrate was washed with water, dried and concentrated. The residue was purified by preparative HPLC and the appropriate effluent fractions were made basic with 1 M aqueous sodium hydroxide and extracted twice with DCM. The combined organic phases were washed with water, dried and concentrated to provide 4-(3-(3,4-dimethyl-2-oxopyrrolidin-1-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide as a white solid (11 mg, 55%), which was a mixture of diastereomers. Mass spectrum m/z 452.1 (M+H—H2O)+.

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. waitThe mixture was again stirred overnight
  3. filtrationfiltered through Celite
  4. washThe filtrate was washed with water
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC
  8. extractionextracted twice with DCM
  9. washThe combined organic phases were washed with water
  10. customdried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c64b8144d1c946b2af4bff75304053f0
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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