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 403254ノート

反応式

HRID 403254 の反応式
[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

参加物

7

反応物 4

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

生成物 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-one収率 87.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
23 °C

実験手順

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)+].

後処理

  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

出典と根拠

ORDレコード
ord-054a38bd023a4888abeb8569f8f71e37
出典データセット
uspto-grants-2014_06
特許番号
US08748418B2

反応ノート

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