Methyl 3-mercaptopropionate → Tert-butyl 4-((2-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate

HRID 335262ノート

反応式

HRID 335262 の反応式
Br[C:2]1[CH:3]=[C:4]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[N:13]=2)=[N:6][CH:7]=1.C(N(C(C)C)C(C)C)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(CC)(CC)C=3C=CC=2)C=CC=CC=1.[SH:88][CH2:89][CH2:90][C:91]([O:93][CH3:94])=[O:92]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O1CCOCC1>[CH3:94][O:93][C:91](=[O:92])[CH2:90][CH2:89][S:88][C:2]1[CH:3]=[C:4]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[N:13]=2)=[N:6][CH:7]=1

参加物

8

反応物 4

HCID 18050Methyl 3-mercaptopropionateHCID 81531DiisopropylethylamineHCID 57742615Tert-butyl 4-((2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylateHCID 866782334,5-bis(diphenylphosphino)-9,9-diethyl-9H-xanthene

生成物 1

HCID 57742831Tert-butyl 4-((2-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate収率 94.5%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
95 °C

実験手順

The atmosphere above a mixture of tert-butyl 4-((2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate (1.52 g, 2.79 mmol), N-ethyl-N-isopropylpropan-2-amine (0.971 mL, 5.57 mmol), 4,5-bis(diphenylphosphino)-9,9-diethyl-9H-xanthene (0.161 g, 0.279 mmol), and dioxane (25 mL) was purged with nitrogen. Methyl 3-mercaptopropanoate (0.332 mL, 3.07 mmol) and Pd2dba3 (0.128 g, 0.139 mmol) were added, and the reaction was heated at 95° C. overnight. The reaction was cooled to ambient temperature and filtered through celite. The filtrate was concentrated and purified by MPLC (Biotage) eluting with 3:2 hexane:ethyl acetate to afford the title compound (1.54 g, 94.5% yield) as a tacky white solid: 1H NMR (CDCl3) δ 8.70 (s, 1H), 8.16 (s, 1H), 7.40 (t, 2H), 7.24 (t, 1H), 7.14 (s, 1H), 7.06 (d, 2H), 6.46 (s, 1H), 4.08 (m, 2H), 3.65 (s, 3H), 2.99 (t, 2H), 2.67 (m, 2H), 2.56 (d, 2H), 2.55 (t, 2H), 1.85 (m, 1H), 1.66 (m, 2H), 1.45 (s, 9H), 1.16 (m, 2H).

後処理

  1. customwas purged with nitrogen
  2. temperatureThe reaction was cooled to ambient temperature
  3. filtrationfiltered through celite
  4. concentrationThe filtrate was concentrated
  5. custompurified by MPLC (Biotage)
  6. washeluting with 3:2 hexane

出典と根拠

ORDレコード
ord-f8da8bb3fe3c4f5ea05c331e8e912b26
出典データセット
uspto-grants-2014_11
特許番号
US08883828B2

反応ノート

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