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2-(Methylthio)-4-(tributylstannyl)pyrimidine → 2-(S)-{[4-(4-Methoxy-phenoxy)-2'-methylsulfanyl-[2,4]bipyrimidin-yl-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2359640
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HRID 2359640 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH:14][C:15]1[C:16]([O:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[N:17][C:18](Cl)=[N:19][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:31][S:32][C:33]1[N:38]=[C:37]([Sn](CCCC)(CCCC)CCCC)[CH:36]=[CH:35][N:34]=1>O1CCOCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH:14][C:15]1[C:16]([O:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[N:17][C:18]([C:35]2[CH:36]=[CH:37][N:38]=[C:33]([S:32][CH3:31])[N:34]=2)=[N:19][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
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참가 물질

5

반응물 2

HCID 27632612-(Methylthio)-4-(tributylstannyl)pyrimidine2회HCID 582430462-(S)-{[2-Chloro-4-(4-methoxy-phenoxy)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 582474432-(S)-{[4-(4-Methoxy-phenoxy)-2'-methylsulfanyl-[2,4]bipyrimidin-yl-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester수율 50.2%

시약·촉매·용매 2

HCID 8857
Ethyl Acetate
용매
HCID 312751,4-Dioxane용매

실험 절차

To a teflon-lined septum-sealed Schlenk tube, a mixture of Compound 1e (213 mg; 0.49 mmol), 2-methylsulfanyl-4-tributylstannanyl-pyrimidine (Compound 7a) (305 mg; 0.735 mmol) and tetrakis-(triphenylphosphine)palladium(0) (57 mg; 0.049 mmol) in dioxane (1.0 mL) was irradiated in a Microwave reactor at 150° C. for 30 min. The resultant mixture was diluted with EtOAc, and washed with saturated NH4Cl(aq) and H2O. The organic phase was washed with H2O, and then dried over Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a heptane-EtOAc gradient to afford Compound 7b (129 mg; 50% yield). 1H-NMR (400 MHz, CDCl3): δ 8.48-8.50 (m, 1H), 8.08-8.12 (m, 1H), 7.54-7.57 (m, 1H), 7.16-7.23 (m, 2H), 6.96-7.01 (m, 2H), 6.27 (br. s, 0.7H), 5.18 (br, 0.3H), 4.25-4.36 (m, 1H), 3.88 (s, 3H), 3.24-3.59 (m, 4H), 2.68 (s, 3H), 1.79-2.16 (m, 4H), 1.44-1.54 (m, 9H); MS: m/z 525.2 (M+H)+.

후처리

  1. customwas irradiated in a Microwave reactor at 150° C. for 30 min
  2. washwashed with saturated NH4Cl(aq) and H2O
  3. washThe organic phase was washed with H2O
  4. dry with materialdried over Na2SO4
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated under reduced pressure
  7. customto give the crude material
  8. customThe crude material was purified by flash column chromatography (SiO2)
  9. washeluting with a heptane-EtOAc gradient

출처 및 근거

ORD 기록
ord-5a9c747c1b7347daba70a37477d3998a
출처 데이터셋
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08685990B2

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