1-Methylpyrrolidine → 4-(2-(((3,3-Bis(4-fluorophenyl)propyl)(cyclopropyl)carbamoyl)amino)-5-chloro-1,3-thiazol-4-yl)benzenesulfonamide

HRID 2190351Notes

Reaction equation

HRID 2190351 reaction equation
[NH2:1][C:2]1[S:3][C:4]([Cl:17])=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH2:16])(=[O:15])=[O:14])=[CH:9][CH:8]=2)[N:6]=1.Cl[C:19](OC1C=CC=CC=1)=[O:20].CN1CCCC1.Cl.[F:35][C:36]1[CH:41]=[CH:40][C:39]([CH:42]([C:49]2[CH:54]=[CH:53][C:52]([F:55])=[CH:51][CH:50]=2)[CH2:43][CH2:44][NH:45][CH:46]2[CH2:48][CH2:47]2)=[CH:38][CH:37]=1>CN(C=O)C.N1C=CC=CC=1>[F:35][C:36]1[CH:41]=[CH:40][C:39]([CH:42]([C:49]2[CH:50]=[CH:51][C:52]([F:55])=[CH:53][CH:54]=2)[CH2:43][CH2:44][N:45]([CH:46]2[CH2:47][CH2:48]2)[C:19]([NH:1][C:2]2[S:3][C:4]([Cl:17])=[C:5]([C:7]3[CH:8]=[CH:9][C:10]([S:13]([NH2:16])(=[O:15])=[O:14])=[CH:11][CH:12]=3)[N:6]=2)=[O:20])=[CH:38][CH:37]=1

Participants

7

Reactant 4

HCID 84541-MethylpyrrolidineHCID 15891Phenyl chloroformateHCID 575863244-(2-Amino-5-chlorothiazol-4-yl)benzenesulfonamideHCID 68725432N-(3,3-bis(4-fluorophenyl)propyl)cyclopropanamine hydrochloride

Product 1

HCID 575863804-(2-(((3,3-Bis(4-fluorophenyl)propyl)(cyclopropyl)carbamoyl)amino)-5-chloro-1,3-thiazol-4-yl)benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(2-amino-5-chlorothiazol-4-yl)benzenesulfonamide (318 mg, 1097 μmol) and pyridine (266 μl, 3292 lμmol) in DMF (10 mL) was chilled to 0° C. To this solution was added slowly phenyl chloroformate (131 μl, 1043 μmol) via syringe. The mixture was slowly warmed to RT, and stirred for 2 hr. At this point, 1-methylpyrrolidine (342 μl, 3292 μmol) and N-(3,3-bis(4-fluorophenyl)propyl)cyclopropanamine hydrochloride (338 mg, 1043 μmol) were added consecutively to the reaction mixture. The mixture was heated to 80° C. and was stirred overnight. Volatiles were removed by concentration under reduced pressure. The leftover residue was solubilized with 100 mL of a 1:1 mixture of water and ethyl acetate. The organic phase was separated and the aqueous phase was extracted further with ethyl acetate (2×75 mL). The combined organic extracts were dried with magnesium sulfate, filtered, and concentrated. Purification by chromatography on silica (eluted with EtOAc/Hexanes) gave 4-(2-(((3,3-bis(4-fluorophenyl)propyl)(cyclopropyl)carbamoyl)amino)-5-chloro-1,3-thiazol-4-yl)benzenesulfonamide 182. Mass spectrum, calculated for C28H25ClF2N4O3S2 602. 1; found 603.1 (M++1).

Workup

  1. temperatureThe mixture was heated to 80° C.
  2. stirringwas stirred overnight
  3. customVolatiles were removed by concentration under reduced pressure
  4. additionThe leftover residue was solubilized with 100 mL of a 1:1 mixture of water and ethyl acetate
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted further with ethyl acetate (2×75 mL)
  7. dry with materialThe combined organic extracts were dried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by chromatography on silica (eluted with EtOAc/Hexanes)

Sources & evidence

ORD record
ord-0b26fb98ee614dc3813456f8d564c981
Source dataset
uspto-grants-2012_12
Patent number
US08324396B2

Reaction notes

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