Methanesulfonyl chloride → HCID 16722642, compound

HRID 1983101Notes

Reaction equation

HRID 1983101 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH2:26])[CH:6]=[CH:7][C:8]=1[C:9]1[O:10][C:11]([C:14]2[C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:16][O:17][C:18]=2[CH3:19])=[N:12][N:13]=1.C(N(CC)C(C)C)(C)C.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C1COCC1.CN(C)C1C=CN=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:26]([S:37]([CH3:36])(=[O:39])=[O:38])[S:37]([CH3:36])(=[O:39])=[O:38])[CH:6]=[CH:7][C:8]=1[C:9]1[O:10][C:11]([C:14]2[C:15]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[N:16][O:17][C:18]=2[CH3:19])=[N:12][N:13]=1

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 167225873-Methoxy-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenylamine

Product 1

HCID 16722642HCID 16722642, compoundYield 117.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-methoxy-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenylamine (200 mg, 0.57 mmol) in THF (2 mL) were added N,N-diisopropyl ethyl amine (0.15 mL, 0.86 mmol), 4-dimethylaminopyridine (8 mg, 0.06 mmol) and methanesulfonyl chloride (53 μL, 0.69 mmol). The resulting suspension was then stirred for 18 h at ambient temperature. Further N,N-diisopropyl ethyl amine (0.15 mL, 0.86 mmol) and methanesulfonyl chloride (54 μL, 0.689 mmol) was added and stirred was continued for 24 h at 50° C. The reaction mixture was extracted with aqueous HCl (1 M, 15 mL) and ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers were washed with brine (half-saturated, 20 mL) and aqueous sodium carbonate (saturated, 20 mL). Drying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=60:20:20 to 0:80:20) afforded the title compound (205 mg, 71%) as a white solid. MS: m/e=505.0 [M+H]+.

Workup

  1. stirringstirred
  2. waitwas continued for 24 h at 50° C
  3. extractionThe reaction mixture was extracted with aqueous HCl (1 M, 15 mL) and ethyl acetate (20 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  5. washthe combined organic layers were washed with brine (half-saturated, 20 mL) and aqueous sodium carbonate (saturated, 20 mL)
  6. dry with materialDrying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=60:20:20 to 0:80:20)

Sources & evidence

ORD record
ord-9816a5438411499488ebb64dc9fd751f
Source dataset
uspto-grants-2009_06
Patent number
US07541372B2

Reaction notes

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