Acetyl chloride → HCID 24759733, compound

HRID 889584Notes

Reaction equation

HRID 889584 reaction equation
C(Cl)(=O)C.[NH:5]1[CH2:10][CH2:9][CH:8]=[C:7]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[NH:13][CH:12]=2)[CH2:6]1>[OH-].[OH-].[Pd+2].CO>[NH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[NH:13][CH:12]=2)[CH2:6]1

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 58172481HCID 58172481, compound

Product 1

HCID 24759733HCID 24759733, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

10 ml acetylchloride was slowly added to 200 ml of MeOH (−10° C.). After 15 minutes, this solution was added to compound 5 (1.43 g, 7.18 mmol) and 20% Pd(OH)2/C (130 mg). The mixture was hydrogenated at 50 psi for 1 hour. The mixture was filtered and concentrated. A subsequent filtration over SCX-2, followed by flash chromatography (MeOH/triethylamine (97/3) afforded compound 6 (0.81 g, 4.02 mmol, 55%) which was reacted with 1 equivalent of fumaric acid in EtOH and concentrated. Recrystallization from EtOH/ethylacetate afforded a solid (free base/fumaric acid (2:1)), mp>225° C. (decomposition). 1H-NMR (400 MHz, D2O): δ 8.04 (bd, J=5 Hz, 1H), 7.93 (bd, J=8 Hz, 1H), 7.13 (bs, 1H), 7.01 (dd, J=8 Hz, 5 Hz, 1H), 6.36 (s, 1H), 3.46-3.40 (m, 1H), 3.37-3.31 (m, 1H), 3.14-3.04 (m, 1H), 2.92-2.82 (m, 2H), 2.0-1.87 (m, 2H), 1.8-1.54 (m, 2H).

Workup

  1. waitThe mixture was hydrogenated at 50 psi for 1 hour
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated
  4. filtrationA subsequent filtration over SCX-2

Sources & evidence

ORD record
ord-f0fce23e298c4944b63b7e441ff3b141
Source dataset
uspto-grants-2012_08
Patent number
US08252930B2

Reaction notes

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