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Cesium carbonate → (3R)-tert-butyl 3-(6-methoxy-2-morpholino-5-(5-(trifluoromethyl)benzo[d]thiazol-2-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate

HRID 1507519
ノート
印刷プレビュー

反応式

HRID 1507519 の反応式
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[CH:5][C:6]2[S:10][CH:9]=[N:8][C:7]=2[CH:11]=1.I[C:15]1[C:16]([NH:29][CH:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)=[N:17][C:18]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[N:19][C:20]=1[O:21][CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=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.[Cu]I>[CH3:22][O:21][C:20]1[N:19]=[C:18]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:17]=[C:16]([NH:29][C@@H:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)[C:15]=1[C:9]1[S:10][C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:12])[F:13])=[CH:11][C:7]=2[N:8]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 199372475-(Trifluoromethyl)-1,3-benzothiazoleHCID 117677619Tert-butyl 3-((5-iodo-6-methoxy-2-morpholinopyrimidin-4-yl)amino)piperidine-1-carboxylate

生成物 1

HCID 89554303(3R)-tert-butyl 3-(6-methoxy-2-morpholino-5-(5-(trifluoromethyl)benzo[d]thiazol-2-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 24350
Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
触媒
HCID 178418397HCID 178418397、化合物触媒
HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

Into a 25-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 5-(trifluoromethyl)-1,3-benzothiazole (100 mg, 0.49 mmol, 1.80 equiv) in N,N-dimethylformamide (5.0 mL), tert-butyl 3-[[5-iodo-6-methoxy-2-(morpholin-4-yl)pyrimidin-4-yl]amino]piperidine-1-carboxylate (140.2 mg, 0.27 mmol, 1.00 equiv), Cesium Carbonate (534.3 mg, 6.00 equiv), Tetrakis(triphenylphosphine)palladium (57.8 mg, 0.05 mmol, 0.18 equiv), and Copper (I) iodide (9.5 mg, 0.05 mmol, 0.18 equiv). The resulting mixture was heated for 2.5 h at 85° C. in an oil bath, cooled down, quenched by the addition of 15 mL of water and then extracted with ethyl acetate (4×15 mL). The combined organic layers were washed with brine (20 mL) and dried over anhydrous sodium sulfate. After filtration and concentration under reducing pressure, the residue was purified by chromatography on a silica gel column eluting with petroleum ether/ethyl acetate (10:1-3:1) to afford the title compound as a gray white solid. MS m/z [M+H]+ (ESI): 595

後処理

  1. customInto a 25-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperaturecooled down
  4. customquenched by the addition of 15 mL of water
  5. extractionextracted with ethyl acetate (4×15 mL)
  6. washThe combined organic layers were washed with brine (20 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationAfter filtration and concentration
  9. customthe residue was purified by chromatography on a silica gel column
  10. washeluting with petroleum ether/ethyl acetate (10:1-3:1)

出典と根拠

ORDレコード
ord-6ae727363e0647b1b0aacfa0f26fcb90
出典データセット
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09221809B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート