Xenon difluoride → N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)-benzamide

HRID 1940280노트

반응식

HRID 1940280 반응식
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[NH:8][C:9](=[O:24])[C:10]1[CH:15]=[CH:14][C:13]([S:16][CH3:17])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1.C(C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C.[Xe](F)[F:42]>ClCCl>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[NH:8][C:9](=[O:24])[C:10]1[CH:15]=[CH:14][C:13]([S:16][CH2:17][F:42])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1

참가 물질

5

반응물 3

HCID 83674Xenon difluorideHCID 988982,6-Di-tert-butyl-4-methylpyridineHCID 15458418N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(methylthio)benzamide

생성물 1

HCID 21187859N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)-benzamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(methylthio)benzamide (1 g; that is prepared as described in Example 20) in dichloromethane (100 mL), containing molecular sieve 4A, under nitrogen, is treated with 2,6-di-tert-butyl-4-methylpyridine (1.28 g). The resulting mixture is stirred at room temperature for 1.5 hours, and then it is cooled to 0° C. (in an ice/salt bath) and treated with xenon difluoride (0.51 g) in one portion. After stirring for a further 2 hours in the cold, the mixture is filtered, and the flitrate is washed with saturated aqueous ammonium chloride solution. The organic phase is dried over sodium sulfate and evaporated. The resulting residue is subjected to flash chromatography, eluting with a mixture of ethyl acetate and pentane (2:3 v/v), to give impure N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)-benzamide (600 mg). It is further purified by reversed phase HPLC on octadecylsilyl silica gel, eluting with a mixture of methanol and water (7:3 v/v), to give N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)benzamide (519 mg), in the form of a white solid, m.p. 111°-113° C. [Elemental analysis: C,51.50; H,4.12; N,6.74%; calculated: C,52.05; H,4.12; N ,6.74%].

후처리

  1. customthat is prepared
  2. temperatureit is cooled to 0° C. (in an ice/salt bath)
  3. stirringAfter stirring for a further 2 hours in the cold, the mixture
  4. filtrationis filtered
  5. washthe flitrate is washed with saturated aqueous ammonium chloride solution
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. customevaporated
  8. washeluting with a mixture of ethyl acetate and pentane (2:3 v/v)

출처 및 근거

ORD 기록
ord-1becd86ab92240e195c159113a1f55ac
출처 데이터셋
uspto-grants-1997_12
특허 번호
US05698711

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