Methanol → Ethyl 4-ethyl-1-(5-(2-(3-ethylureido)-7-propionylbenzo[d]thiazol-5-yl)pyrimidin-2-yl)piperidine-4-carboxylate

HRID 712341ノート

反応式

HRID 712341 の反応式
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([C:22](=[O:25])[CH2:23][CH3:24])[C:10]2[S:14][C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:12][C:11]=2[CH:21]=1)(=O)=O.[CH3:28]O.[CH3:30][C:31]1([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:36][CH2:35][N:34]([C:37]2[N:42]=[CH:41][C:40](B3OC(C)(C)C(C)(C)O3)=[CH:39][N:38]=2)[CH2:33][CH2:32]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1>[CH2:30]([C:31]1([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:32][CH2:33][N:34]([C:37]2[N:38]=[CH:39][C:40]([C:7]3[CH:8]=[C:9]([C:22](=[O:25])[CH2:23][CH3:24])[C:10]4[S:14][C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:12][C:11]=4[CH:21]=3)=[CH:41][N:42]=2)[CH2:35][CH2:36]1)[CH3:28]

参加物

6

反応物 4

HCID 887MethanolHCID 62657Potassium Phosphate, TribasicHCID 66976878Ethyl 4-methyl-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidine-4-carboxylateHCID 866640502-(3-Ethylureido)-7-propionylbenzo[d]thiazol-5-yl trifluoromethanesulfonate2 回

生成物 1

HCID 86664049Ethyl 4-ethyl-1-(5-(2-(3-ethylureido)-7-propionylbenzo[d]thiazol-5-yl)pyrimidin-2-yl)piperidine-4-carboxylate収率 35%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

To a solution of 2-(3-ethylureido)-7-propionylbenzo[d]thiazol-5-yl trifluoromethanesulfonate (Intermediate 13) (0.25 g, 0.587 mmol) in 1,4-dioxane:MeOH (21 mL: 14 mL) were added ethyl 4-methyl-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidine-4-carboxylate (0.46 g, 1.17 mmol) and potassium phosphate (0.19 g, 0.88 mmol) at rt under N2 atmosphere. The reaction mixture was degassed by N2 for 15 min followed by addition of tetrakis (triphenylphosphine)palladium(0) (0.068 g, 0.058 mmol). The reaction mixture was further degassed by N2 for 15 min then stirred for 2 h at 80° C. After the completion of reaction (by TLC), water (50 mL) was added, extracted with EtOAc (3×50 mL) and the combined organic layers washed with water, brine, dried over anhydrous Na2SO4, filtered then concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 100-200 M, 70% EtOAc-hexane) to afford the desired product as an off-white solid (0.110 g, 35%). 1H NMR (DMSO-d6): δ 10.70 (br s, 1H), 8.87 (s, 2H), 8.23 (s, 1H), 8.14 (s, 1H), 6.80 (br s, 1H), 4.47 (m, 2H), 4.17 (q, J=7.20 Hz, 2H), 3.33 (m, 2H), 3.12-3.22 (m, 4H), 2.09 (m, 2H), 1.56 (q, J=7.60 Hz, 2H), 1.39 (m, 2H), 1.22 (t, J=7.20 Hz, 3H), 1.16 (t, J=7.2 Hz, 3H), 1.10 (t, J=7.2 Hz, 3H) and 0.75 (t, J=7.2 Hz, 3H). MS: 539.52 [M+H]+

後処理

  1. customThe reaction mixture was degassed by N2 for 15 min
  2. customThe reaction mixture was further degassed by N2 for 15 min
  3. customAfter the completion of reaction (by TLC), water (50 mL)
  4. additionwas added
  5. extractionextracted with EtOAc (3×50 mL)
  6. washthe combined organic layers washed with water, brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationthen concentrated under reduced pressure
  10. customThe residue was purified by column chromatography (silica gel 100-200 M, 70% EtOAc-hexane)

出典と根拠

ORDレコード
ord-252a85a64a594ef0bfc3697723709003
出典データセット
uspto-grants-2015_11
特許番号
US09181234B2

反応ノート

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