Sodium Bicarbonate → (5R)-5-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one

HRID 403254노트

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HRID 403254 반응식
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:6](=O)[CH2:7][CH2:8][C:9]=2[CH:10]=1.[NH2:12][C:13]1[CH:14]=[CH:15][C:16]([F:30])=[C:17]([C@:19]2([CH3:29])[C:25]([F:27])([F:26])[CH2:24][O:23][CH2:22][C:21](=[O:28])[NH:20]2)[CH:18]=1.[B][B][B][B][B][B][B][B][B][B].C([O-])(O)=O.[Na+]>CO.ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[CH2:8][CH2:7][CH:6]([NH:12][C:13]3[CH:14]=[CH:15][C:16]([F:30])=[C:17]([C@:19]4([CH3:29])[C:25]([F:26])([F:27])[CH2:24][O:23][CH2:22][C:21](=[O:28])[NH:20]4)[CH:18]=3)[C:5]2=[N:4][CH:3]=1

참가 물질

7

반응물 4

HCID 516892Sodium BicarbonateHCID 58082858HCID 58082858, 화합물HCID 68226741(R)-5-(5-amino-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-oneHCID 178419135HCID 178419135, 화합물

생성물 1

HCID 68226747(5R)-5-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one수율 87.2%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

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온도
23 °C

실험 절차

To a solution of 3-chloro-5,6-dihydro-[1]pyrindin-7-one (28 mg, 167 μmol) in methanol (6 ml) and dichloromethane (750 μl) at 23° C. was added (R)-5-(5-amino-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one (intermediate A21A) (49.9 mg, 182 μmol) followed by decaborane (5.6 mg, 167 μmol) and the mixture was stirred at 23° C. for 22 hours. After completion, the mixture was poured into aqueous NaHCO3 solution, extracted with ethyl acetate, the organic layers were dried over Na2SO4 and the solvent evaporated. The crude material was purified by silica gel flash chromatography with n-heptane/ethyl acetate to give the (5R)-5-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one (62 mg, 87%) as an orange solid. MS (ISP): m/z=426.1 [(M+H)+] and 428.1 [(M+2+H)+].

후처리

  1. extractionextracted with ethyl acetate
  2. dry with materialthe organic layers were dried over Na2SO4
  3. customthe solvent evaporated
  4. customThe crude material was purified by silica gel flash chromatography with n-heptane/ethyl acetate

출처 및 근거

ORD 기록
ord-054a38bd023a4888abeb8569f8f71e37
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748418B2

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