Dimethylformamide → 2-{2-[7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetamide

HRID 2239129Notes

Reaction equation

HRID 2239129 reaction equation
[CH3:1][N:2]([S:26]([C:29]1[S:30][CH:31]=[CH:32][CH:33]=1)(=[O:28])=[O:27])[C:3]1[CH:4]=[C:5]([O:21][C:22]([F:25])([F:24])[F:23])[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([OH:20])=O)[CH2:15][N:16]=1)=[CH:8]2.Cl.C[N:36](C)CCCN=C=NCC.CN(C)C=O>O>[CH3:1][N:2]([S:26]([C:29]1[S:30][CH:31]=[CH:32][CH:33]=1)(=[O:28])=[O:27])[C:3]1[CH:4]=[C:5]([O:21][C:22]([F:24])([F:25])[F:23])[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([NH2:36])=[O:20])[CH2:15][N:16]=1)=[CH:8]2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 57476346{2-[7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid

Product 1

HCID 248995172-{2-[7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetamideYield 43%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of {2-[7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (210 mg), 1H-1,2,3-benzotriazol-1-ol-ammonia complex (90 mg), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (120 mg) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 15 hr. 1H-1,2,3-Benzotriazol-1-ol-ammonia complex (150 mg) and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (190 mg) were added to the reaction mixture, and the mixture was further stirred at room temperature for 6 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with aqueous citric acid solution, saturated aqueous sodium hydrogencarbonate and saturated brine, dried (MgSO4), and concentrated. The residue was purified by preparative HPLC to give the title compound (90 mg, yield 43%) as pale-yellow crystals. The crystals were recrystallized from ethyl acetate-hexane to give pale-yellow prism crystals. melting point 186-187° C. MS: 519 (MH+).

Workup

  1. stirringthe mixture was further stirred at room temperature for 6 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed successively with aqueous citric acid solution, saturated aqueous sodium hydrogencarbonate and saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-40065b06c1e04ea3bfddc65f2b1391a3
Source dataset
uspto-grants-2010_05
Patent number
US07718798B2

Reaction notes

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