Tert-butyl 1-(6-(tributylstannyl)pyrazin-2-yl)piperidin-3-ylcarbamate → tert-butyl 3-(6-(3-(tert-butoxycarbonylamino)piperidin-1-yl)pyrazin-2-yl)-5-(2,6-difluorophenyl)-1H-indole-1-carboxylate

HRID 1529294ノート

反応式

HRID 1529294 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:13]=[C:12]2I.C([Sn](CCCC)(CCCC)[C:31]1[N:36]=[C:35]([N:37]2[CH2:42][CH2:41][CH2:40][CH:39]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH2:38]2)[CH:34]=[N:33][CH:32]=1)CCC>CN(C=O)C.C(Cl)Cl.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>[C:46]([O:45][C:44]([NH:43][CH:39]1[CH2:40][CH2:41][CH2:42][N:37]([C:35]2[N:36]=[C:31]([C:12]3[C:11]4[C:15](=[CH:16][CH:17]=[C:9]([C:3]5[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=5[F:8])[CH:10]=4)[N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:13]=3)[CH:32]=[N:33][CH:34]=2)[CH2:38]1)=[O:50])([CH3:49])([CH3:47])[CH3:48]

参加物

8

反応物 2

HCID 67958112Tert-butyl 1-(6-(tributylstannyl)pyrazin-2-yl)piperidin-3-ylcarbamateHCID 67958266tert-butyl 5-(2,6-difluorophenyl)-3-iodo-1H-indole-1-carboxylate

生成物 1

HCID 86709766tert-butyl 3-(6-(3-(tert-butoxycarbonylamino)piperidin-1-yl)pyrazin-2-yl)-5-(2,6-difluorophenyl)-1H-indole-1-carboxylate

試薬・触媒・溶媒 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

A glass microwave reaction vessel was charged with tert-butyl 5-(2,6-difluorophenyl)-3-iodo-1H-indole-1-carboxylate (350 mg, 0.769 mmol), tert-butyl 1-(6-(tributylstannyl)pyrazin-2-yl)piperidin-3-ylcarbamate (436 mg, 0.769 mmol), Pd(PPh3)4 (89 mg, 0.077 mmol), and CuI (15 mg, 0.077 mmol) in DMF (6 mL). The reaction mixture was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 30 min. The mixture was diluted with DCM and water. The organic layer was separated, washed with water and brine, dried over Na2SO4, filtered and concentrated to give the crude product, tert-butyl 3-(6-(3-(tert-butoxycarbonylamino)piperidin-1-yl)pyrazin-2-yl)-5-(2,6-difluorophenyl)-1H-indole-1-carboxylate. MS (ESI, pos. ion) m/z: 606 (M+1). To a solution of tert-butyl 3-(6-(3-(tert-butoxycarbonylamino)piperidin-1-yl)pyrazin-2-yl)-5-(2,6-difluorophenyl)-1H-indole-1-carboxylate (466 mg, 0.769 mmol) in DCM (6 mL) was added TFA (4 mL) and the reaction was stirred at RT for 3 h, then solvent was removed. The residue was diluted with DCM and washed with saturated NaHCO3 aqueous solution twice. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified with RP-HPLC to give 1-(6-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrazin-2-yl)piperidin-3-amine as a light brown solid. MS (ESI, pos. ion) m/z: 406 (M+1).

後処理

  1. customA glass microwave reaction vessel
  2. customThe organic layer was separated
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-a60e3562fa8f463e9fcb7966ca9ca05a
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

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