4-Toluenesulfonyl chloride → 1,3-Dihydro-3-(RS)-(4-methylphenylsulfonyl)amino-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one

HRID 620571Notes

Reaction equation

HRID 620571 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[NH:4][C:3]1=[O:20].[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:31][C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH:1][CH:2]2[N:8]=[C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[F:15])[C:6]3[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=3[NH:4][C:3]2=[O:20])(=[O:29])=[O:28])=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 156371501,3-dihydro-5-(2-fluorophenyl)-3-amino-2H-1,4-benzodiazepin-2-one

Product 1

HCID 156147571,3-Dihydro-3-(RS)-(4-methylphenylsulfonyl)amino-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-oneYield 109.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,3-Dihydro-3-(RS)-amino-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (116 mg, 0.43 mmole) and p-toluenesulfonyl chloride (82 mg, 0.43 mmole) were combined at room temperature in 5 ml of methylene chloride. The pH of the reaction mixture was then adjusted to 8.5 with triethylamine and stirring was continued at room temperature overnight. The reaction mixture was partitioned between methylene chloride and 10% citric acid solution. The phases were separated and the organic layer was washed in succession with 10% citric acid solution (1×30 ml), saturated sodium bicarbonate solution (2×30 ml) and brine. The dried (MgSO4) extracts were concentrated to yield 200 mg of crude product. Recrystallization from ethyl acetate afforded the analytical sample as white needles, m.p. 215°-216° C. HPLC: Greater than 99% pure.

Workup

  1. customThe reaction mixture was partitioned between methylene chloride and 10% citric acid solution
  2. customThe phases were separated
  3. washthe organic layer was washed in succession with 10% citric acid solution (1×30 ml), saturated sodium bicarbonate solution (2×30 ml) and brine
  4. dry with materialThe dried (MgSO4) extracts
  5. concentrationwere concentrated

Sources & evidence

ORD record
ord-1e6ac34853d64642a06d3c21187a34ec
Source dataset
uspto-grants-1989_04
Patent number
US04820834

Reaction notes

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