Acetic Acid → HCID 57797835, compound

HRID 1948867Notes

Reaction equation

HRID 1948867 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[N:12]=[C:13]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[CH:18]=4)[N:14]=[CH:15][C:10]=3[CH2:9][N:8]=[C:7]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[F:33])[C:6]=2[CH:34]=1.C(O)(=O)C>ClCCl.[Zn]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[N:12]=[C:13]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[CH:18]=4)[N:14]=[CH:15][C:10]=3[CH2:9][NH:8][CH:7]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[F:33])[C:6]=2[CH:34]=1

Participants

5

Reactant 2

HCID 176Acetic Acid2×HCID 57797803HCID 57797803, compound

Product 1

HCID 57797835HCID 57797835, compoundYield 67.1%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

[9-Chloro-7-(2-fluoro-phenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl]-(3,4-dimethoxy-phenyl)-amine (I-71, 49 mg, 0.10 mmol) was dissolved in dichloromethane (1.8 mL). Acetic acid (0.43 mL) was added and the solution was stirred and cooled to 0° C. Zinc dust (20 mg, 0.31 mmol) was then added and the mixture was stirred at 0° C. for 1 hour and then allowed to warm to room temperature and stir for 4 hours. Additional zinc dust (10 mg, 0.15 mmol) and acetic acid (0.22 mL) was added and the mixture was stirred at room temperature for 20 hours. The reaction mixture was diluted with dichloromethane. The organic layer was separated and washed with 1N NaOH, brine and then dried over magnesium sulfate, filtered and concentrated in vacuo. The yellow powder was purified by column chromatography (silica gel, ethyl acetate) to afford [9-Chloro-7-(2-fluoro-phenyl)-6,7-dihydro-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl]-(3,4-dimethoxy-phenyl)-amine (I-72) as an orange solid (32 mg, 65%): MS m/z=477.

Workup

  1. stirringthe mixture was stirred at 0° C. for 1 hour
  2. temperatureto warm to room temperature
  3. stirringstir for 4 hours
  4. stirringthe mixture was stirred at room temperature for 20 hours
  5. customThe organic layer was separated
  6. washwashed with 1N NaOH, brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe yellow powder was purified by column chromatography (silica gel, ethyl acetate)

Sources & evidence

ORD record
ord-96b1a5ddc8e84e6fb36f43f5da89de8e
Source dataset
uspto-grants-2013_03
Patent number
US08399659B2

Reaction notes

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