Acetic Acid → 3-(5-(2-Chloropyrimidin-4-yl)-2-morpholinothiazol-4-yl)-2-methoxyaniline

HRID 239356

반응식

HRID 239356 반응식
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([O:32][CH3:33])=[C:21]([NH:25]C(=O)OCC=C)[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1.C(O)(=O)C.C([SnH](CCCC)CCCC)CCC>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[N:10][C:9]=2[C:19]2[C:20]([O:32][CH3:33])=[C:21]([CH:22]=[CH:23][CH:24]=2)[NH2:25])[CH:5]=[CH:4][N:3]=1

참가 물질

6

반응물 3

HCID 176Acetic AcidHCID 5948TributylstannaneHCID 579897552-Propen-1-yl[3-[5-(2-chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-(methyloxy)phenyl]carbamate

생성물 1

HCID 579897953-(5-(2-Chloropyrimidin-4-yl)-2-morpholinothiazol-4-yl)-2-methoxyaniline수율 79.1%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 6344Dichloromethane용매

실험 절차

To a solution of 2-propen-1-yl [3-[5-(2-chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-(methyloxy)phenyl]carbamate (40 g, 99 mmol) in DCM (500 mL), acetic acid (11.3 mL, 197 mmol) and Pd(PPh3)2Cl2 (1.3 g, 1.64 mmol) were added. Then tri-n-butyl tin hydride (37.3 mL, 145 mmol) was added dropwise to the mixture at 0° C. The mixture was stirred at rt for 30 min. The reaction was quenched by slow addition of saturated NaHCO3 (200 mL). The two layers were separated. The aqueous layer was extracted with DCM (400 mL×2). The combined organic layers were washed with water and brine successively, dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product, which was washed with petroleum ether (500 mL) to afford the title compound of Step B (26.1 g, 79.1% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.10 (d, J=5.5 Hz, 1H), 7.01 (dd, J=7.5 Hz, 8.1 Hz, 1H), 6.83 (dd, J=1.5 Hz, 8.2 Hz, 1H), 6.68 (dd, J=1.5 Hz, 7.5 Hz, 1H), 6.61 (d, J=5.5 Hz, 1H), 3.86-3.95 (br, 2H), 3.78-3.82 (m, 4H), 3.58-3.63 (m, 4H), 3.56 (s, 3H).

후처리

  1. customThe reaction was quenched by slow addition of saturated NaHCO3 (200 mL)
  2. customThe two layers were separated
  3. extractionThe aqueous layer was extracted with DCM (400 mL×2)
  4. washThe combined organic layers were washed with water and brine successively
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product, which
  9. washwas washed with petroleum ether (500 mL)

출처 및 근거

ORD 기록
ord-25714ad5d9ab469a9da0428c2ab236a2
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642759B2

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