1,2-Dichloroethane → HCID 22224933, compound

HRID 859612Notes

Reaction equation

HRID 859612 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-yl]-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 tide compound as light yellow solid (49 mg). MS (ISN) 411.2 [(M−H)−]; mp 266–268° C.

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-5021bcea2ddb4ba79fca4d44abe3c976
Source dataset
uspto-grants-2006_12
Patent number
US07151098B2

Reaction notes

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