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

HRID 712341노트

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HRID 712341 반응식
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]

참가 물질

6

반응물 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 trifluoromethanesulfonate2회

생성물 1

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

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

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]+

후처리

  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)

출처 및 근거

ORD 기록
ord-252a85a64a594ef0bfc3697723709003
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181234B2

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