Benzoyl chloride → HCID 178504914, compound

HRID 1282701Notes

Reaction equation

HRID 1282701 reaction equation
[C:1]([Cl:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH:11]1[CH:15]=[C:14]([CH2:16][N:17]2[C:23]3[CH:24]=[CH:25][C:26]([C:28]#[N:29])=[CH:27][C:22]=3[CH2:21][N:20]([S:30]([CH3:33])(=[O:32])=[O:31])[C@H:19]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:18]2)[N:13]=[CH:12]1.[CH3:41]CN(C(C)C)C(C)C.[C:50]([O-])([OH:52])=[O:51].[Na+]>ClCCl.C(Cl)(Cl)Cl>[C:28]([C:26]1[CH:25]=[CH:24][C:23]2[N:17]([CH2:16][C:14]3[N:13]=[CH:12][N:11]([C:50]([O:52][C:2]([CH3:7])([CH3:3])[CH3:1])=[O:51])[CH:15]=3)[CH2:18][C@@H:19]([CH2:34][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:20]([S:30]([CH3:33])(=[O:31])=[O:32])[CH2:21][C:22]=2[CH:27]=1)#[N:29].[ClH:9].[NH:11]1[CH:15]=[C:14]([CH2:16][N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21][N:20]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:19][CH:18]2[CH2:41][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[N:13]=[CH:12]1

Participants

8

Reactant 4

HCID 7412Benzoyl chloride2×HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 178504922HCID 178504922, compound

Product 2

HCID 69841490(R)-7-cyano-2,3,4,5-tetrahydro-1-[(((1,1-dimethylethoxy)-carbonyl)-1H-imidazol-4-yl)methyl]-4-(methylsulfonyl)-3-(phenylmethyl)-1H-1,4-benzodiazepineHCID 178504914HCID 178504914, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

Benzoyl chloride (2.2 mL, 1.9 mmol) was added to a solution of Compound C of Example 248 and DIEA (0.32 mL, 1.99 mmol) in dichloromethane (3 mL) at 0° C. under argon. The solution was slowly warmed to rt. At 15 and 30 hr, 0.5 equivalents of benzoyl chloride and DIEA were added. After stirring for 2 days, the mixture was diluted with chloroform (20 mL) and NaHCO3 (5 mL). The layers were separated, the aqueous layer was extracted with chloroform (2×15 mL). The combined organic extracts were washed with NaHCO3 (2×5 mL), water (1×10 mL) and brine (2×10 mL), dried over MgSO4, filtered and concentrated. The residue was purified on a flash column eluting with 20% and 30% EtOAc in hexane to afford Compound A as a yellow oil 2 (0.21 g, 77%). MS (M+H)+ 368.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with chloroform (2×15 mL)
  3. washThe combined organic extracts were washed with NaHCO3 (2×5 mL), water (1×10 mL) and brine (2×10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on a flash column
  8. washeluting with 20% and 30% EtOAc in hexane

Sources & evidence

ORD record
ord-4264b650488047c4bbd643228f383c89
Source dataset
uspto-grants-2002_09
Patent number
US06455523B1

Reaction notes

Loading…