Water → 3-{[(5-Chloro-thiophene-2-carbonyl)-amino]-methyl}-[1,2,4]oxadiazole-5-carboxylic acid[2-fluoro-4-(2-oxo-2h-pyridin-1-yl)-phenyl]-amide

HRID 2237642노트

반응식

HRID 2237642 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])=[CH:4][C:3]=1[F:15].C[Al](C)C.C([O:22][C:23]([C:25]1[O:29][N:28]=[C:27]([CH2:30][NH:31][C:32]([C:34]2[S:35][C:36]([Cl:39])=[CH:37][CH:38]=2)=[O:33])[N:26]=1)=O)C.O>O1CCOCC1>[F:15][C:3]1[CH:4]=[C:5]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH:6]=[CH:7][C:2]=1[NH:1][C:23]([C:25]1[O:29][N:28]=[C:27]([CH2:30][NH:31][C:32]([C:34]2[S:35][C:36]([Cl:39])=[CH:37][CH:38]=2)=[O:33])[N:26]=1)=[O:22]

참가 물질

6

반응물 4

HCID 962WaterHCID 16682925TrimethylaluminumHCID 221815481-(4-Amino-3-fluorophenyl)pyridin-2-oneHCID 593029563-{[(5-Chloro-thiophene-2-carbonyl)-amino]-methyl}-[1,2,4]oxadiazole-5-carboxylic acid ethyl ester

생성물 1

HCID 247764483-{[(5-Chloro-thiophene-2-carbonyl)-amino]-methyl}-[1,2,4]oxadiazole-5-carboxylic acid[2-fluoro-4-(2-oxo-2h-pyridin-1-yl)-phenyl]-amide

시약·촉매·용매 1

HCID 312751,4-Dioxane용매2회

실험 절차

To a stirred suspension of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (259 mg; CAS 536747-52-1, prepared according to C. F. Bigge et al., patent application WO 2003045912) at r.t. in dioxane (4 ml) under an argon atmosphere was added trimethylaluminium (0.63 ml; 2 M solution in heptane)-->foaming. The mixture was stirred at r.t. for 2 h. A solution of 3-{[(5-chloro-thiophene-2-carbonyl)-amino]-methyl}-[1,2,4]oxadiazole-5-carboxylic acid ethyl ester (100 mg) in dioxane (4 ml) was then added. The mixture was heated to 100° C. over night. The mixture was cooled to r.t. and H2O (0.8 ml) was added (-->bubbling). After 15 min stirring, MgSO4 was added and stirring was continued for another 15 min. The mixture was then filtered and the cake was washed with dichloromethane. The filtrate was concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2->CH2Cl2/MeOH 9:1) to give 3-{[(5-chloro-thiophene-2-carbonyl)-amino]-methyl}-[1,2,4]oxadiazole-5-carboxylic acid[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-amide as light yellow solid. 474.1 ([M+H]+)

후처리

  1. temperatureThe mixture was heated to 100° C. over night
  2. temperatureThe mixture was cooled to r.t.
  3. custom(-->bubbling)
  4. stirringAfter 15 min stirring
  5. additionMgSO4 was added
  6. stirringstirring
  7. waitwas continued for another 15 min
  8. filtrationThe mixture was then filtered
  9. washthe cake was washed with dichloromethane
  10. concentrationThe filtrate was concentrated
  11. customThe crude product was purified by column chromatography (silica gel; gradient: CH2Cl2->CH2Cl2/MeOH 9:1)

출처 및 근거

ORD 기록
ord-3c338cb94d5d4f1999ad714463d03e01
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07718679B2

반응 노트

불러오는 중…