1,2-Dichloroethane → HCID 22224933, compound

HRID 1635477Notes

Reaction equation

HRID 1635477 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:28]=[CH:27][C:11]3[N:12]=[C:13]([C:18]4[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=4)[C:21](O)=[O:22])[CH2:14][C:15](=[O:17])[NH:16][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.C(Cl)CCl.O[NH:44][C:45](=[NH:47])[CH3:46]>CC#N.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:28]=[CH:27][C:11]3[N:12]=[C:13]([C:18]4[CH:26]=[CH:25][CH:24]=[C:20]([C:21]5[O:22][N:47]=[C:45]([CH3:46])[N:44]=5)[CH:19]=4)[CH2:14][C:15](=[O:17])[NH:16][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 22224672HCID 22224672, compoundHCID 178465666HCID 178465666, compound

Product 1

HCID 22224933HCID 22224933, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 21891449acetonitrile N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-[7-(4-fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2]-benzoic acid (Example 163) (262 mg, 0.7 mmol) and 1-hydroxybenzotriazole (130 mg, 0.84 mmol) in CH3CN/DMF (7 mL/10 mL), cooled to 0° C., was added EDC (161 mg, 0.84 mmol) and the mixture was stirred at 0° C. for 1 h. N-hydroxy-acetamidine (62 mg, 0.84 mmol) was added and stirring was continued for 4 h at 23° C. The reaction mixture was partitioned between ethyl acetate and H2O and the organic layer was dried over Na2SO4 and evaporated in vacuum. The residue was heated in toluene (30 mL) for 20 h at reflux. The mixture was cooled, evaporated in vacuum and the residue was chromatographed on silica gel using ethyl acetate/hexane (2:1) as eluent. The purified product was triturated with ethyl acetate to give the title compound as light yellow solid (49 mg).

Workup

  1. stirringstirring
  2. waitwas continued for 4 h at 23° C
  3. customThe reaction mixture was partitioned between ethyl acetate and H2O
  4. dry with materialthe organic layer was dried over Na2SO4
  5. customevaporated in vacuum
  6. temperatureThe residue was heated in toluene (30 mL) for 20 h
  7. temperatureat reflux
  8. temperatureThe mixture was cooled
  9. customevaporated in vacuum
  10. customthe residue was chromatographed on silica gel
  11. customThe purified product was triturated with ethyl acetate

Sources & evidence

ORD record
ord-10f36b07fe2e40f8a8394541d665da33
Source dataset
uspto-grants-2003_01
Patent number
US06509328B1

Reaction notes

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