1,2-Dichloroethane → HCID 59591416, compound

HRID 1666578Notes

Reaction equation

HRID 1666578 reaction equation
[CH2:1]([NH:3][S:4]([C:7]1[C:8]([F:17])=[CH:9][C:10]([F:16])=[C:11]([CH:15]=1)[C:12]([OH:14])=O)(=[O:6])=[O:5])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH:32]1([C:37]2[S:41][C:40]([NH2:42])=[N:39][N:38]=2)[CH2:36][CH2:35][CH2:34][CH2:33]1>CN(C)C=O.ClCCl>[CH:32]1([C:37]2[S:41][C:40]([NH:42][C:12](=[O:14])[C:11]3[CH:15]=[C:7]([S:4]([NH:3][CH2:1][CH3:2])(=[O:5])=[O:6])[C:8]([F:17])=[CH:9][C:10]=3[F:16])=[N:39][N:38]=2)[CH2:33][CH2:34][CH2:35][CH2:36]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 20636875-cyclopentyl-1,3,4-thiadiazol-2-amineHCID 58728142HCID 58728142, compound

Product 1

HCID 59591416HCID 59591416, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

2,4-difluorobenzoic acid (200 mg, 0.765 mmol) in chlorosulfonic acid (1.535 ml, 22.92 mmol) was stirred at room temperature for 30 seconds, then microwave 200 degree for 10 mins. The reaction mixture was cooled to room temperature and dumped on ice (10 g) slowly. Ethyl acetate (25 ml) was added and extracted twice with ethyl acetate (10 mL X2). The combined organic phase was dried over MgSO4. Ethylamine (1833 μl, 3.67 mmol) in THF (2.0 M) was added, stirred at room temperature for 10 mins and washed with 1 N HCl (10 ml). The organic phase was dried over MgSO4 and concentrated to give 5-[(ethylamino)sulfonyl]-2,4-difluorobenzoic acid, which was purified by HPLC 5%-60% CH3CN/H2O TFA (0.1%) to give 60 mg. To 5-[(ethylamino)sulfonyl]-2,4-difluorobenzoic acid in N,N-dimethylformamide (3 ml) and dichloromethane (3 ml) was added to EDC (32.5 mg, 0.170 mmol) and HOBt (26.0 mg, 0.170 mmol). After 10 mins, 5-cyclopentyl-1,3,4-thiadiazol-2-amine was added. The reaction mixture was stirred at rt overnight, concentrated and purifed by HPLC. The solvents were removed and purified by HPLC (30-70% with TFA 0.1% CNCH3 and H2O, 18 mins) to give the title compound (5 mg).

Workup

  1. customwas purified by HPLC 5%-60% CH3CN/H2O TFA (0.1%)
  2. customto give 60 mg
  3. concentrationconcentrated
  4. customThe solvents were removed
  5. custompurified by HPLC (30-70% with TFA 0.1% CNCH3 and H2O, 18 mins)

Sources & evidence

ORD record
ord-57cfc7de0ce34807ae9099168b770415
Source dataset
uspto-grants-2011_10
Patent number
US08044075B2

Reaction notes

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