Sodium Carbonate → HCID 44540258、化合物

HRID 2061817ノート

反応式

HRID 2061817 の反応式
[CH3:1][O:2][CH2:3][CH:4]([N:8]1[C:17]2[C:12](=[CH:13][C:14](I)=[CH:15][CH:16]=2)[C:11](=[O:19])[C:10]([C:20]([N:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]2)=[O:21])=[CH:9]1)[CH2:5][O:6][CH3:7].[CH2:35]([NH:37][C:38]([NH:40][C:41]1[CH:46]=[C:45]([C:47]2[S:48][CH:49]=[C:50]([C:52]([F:55])([F:54])[F:53])[N:51]=2)[C:44](B2OC(C)(C)C(C)(C)O2)=[CH:43][N:42]=1)=[O:39])[CH3:36].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][CH2:3][CH:4]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:44]3[CH:43]=[N:42][C:41]([NH:40][C:38](=[O:39])[NH:37][CH2:35][CH3:36])=[CH:46][C:45]=3[C:47]3[S:48][CH:49]=[C:50]([C:52]([F:55])([F:53])[F:54])[N:51]=3)=[CH:15][CH:16]=2)[C:11](=[O:19])[C:10]([C:20]([N:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]2)=[O:21])=[CH:9]1)[CH2:5][O:6][CH3:7]

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 592084681-Ethyl-3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)urea2 回HCID 59415902HCID 59415902、化合物2 回

生成物 1

HCID 44540258HCID 44540258、化合物収率 49.4%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of tert-butyl 4-{[1-(1,3-dimethoxypropan-2-yl)-6-iodo-4-oxo-1,4-dihydroquinolin-3-yl]carbonyl}piperazine-1-carboxylate (Intermediate 79, 400 mg, 0.68 mmol) in dimethylformamide (15 mL) was purged argon gas, then tetrakis(triphenylphosphine)palladium (69.25 mg, 0.06 mmol) followed by 1-ethyl-3-{5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-2-yl}urea (Intermediate 17, 360 mg, 0.82 mmol) was added. The mixture was stirred at room temperature and sodium carbonate (217 mg, 2.05 mmol) which was dissolved in minimum amount of water was added and the reaction mixture was heated to 95° C. for 3 h. After completion of the reaction, the reaction mixture was cooled to room temperature, filtered through celite, and the filtrate was poured into water (200 mL) and stirred for 30 min. The obtained solid was filtered and dried to give the crude compound. The crude was purified by column chromatography eluting with a gradient of 30% ethyl acetate/petroleum ether to 60% ethyl acetate/petroleum ether to afford 260 mg (49%) of tert-butyl 4-{[1-(1,3-dimethoxypropan-2-yl)-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydroquinolin-3-yl]carbonyl}piperazine-1-carboxylate.

後処理

  1. additionwas added
  2. additionwas added
  3. temperaturethe reaction mixture was heated to 95° C. for 3 h
  4. customAfter completion of the reaction
  5. temperaturethe reaction mixture was cooled to room temperature
  6. filtrationfiltered through celite
  7. additionthe filtrate was poured into water (200 mL)
  8. stirringstirred for 30 min
  9. filtrationThe obtained solid was filtered
  10. customdried
  11. customto give the crude compound
  12. customThe crude was purified by column chromatography
  13. washeluting with a gradient of 30% ethyl acetate/petroleum ether to 60% ethyl acetate/petroleum ether

出典と根拠

ORDレコード
ord-c0e71ae4af9b4877a86e15d0f0507d45
出典データセット
uspto-grants-2012_10
特許番号
US08283361B2

反応ノート

読み込み中…