Potassium Carbonate → 2-(S)-{[4-(4-Methoxy-phenoxy)-2-(5-methylsulfanyl-pyridin-3-yl)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1894143노트

반응식

HRID 1894143 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[CH:34]=[C:35](B(O)O)[CH:36]=[N:37][CH:38]=1.C([O-])([O-])=O.[K+].[K+]>C(O)C.O.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]=[N:37][CH:38]=[C:33]([S:32][CH3:31])[CH:34]=2)=[N:19][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 22392014(5-(Methylsulfanyl)pyridin-3-yl)boronic acid2회HCID 582430462-(S)-{[2-Chloro-4-(4-methoxy-phenoxy)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 582474022-(S)-{[4-(4-Methoxy-phenoxy)-2-(5-methylsulfanyl-pyridin-3-yl)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester수율 72%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

To a teflon-lined septum sealed Schlenk tube, a mixture of Compound 1e (4.0 g; 9.20 mmol), 5-(methylthio)pyridin-3-yl boronic acid (Compound 1f) (2.32 g; 13.7 mmol), K2CO3 (2.50 g; 18.1 mmol) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium(II) (0.45 g, 0.55 mmol) in a mixture of ethanol (18 mL) and H2O (4.5 mL) was irradiated in a microwave reactor at 130° C. for 30 min. The resultant mixture was diluted with EtOAc, 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 1g (3.45 g; 72% yield) as pale-yellow solid. 1H-NMR (400 MHz, CDCl3): δ 9.00 (s, 1H), 8.40 (d, 1H), 8.21 (s, 1H), 7.99 (br. s, 1H), 7.12-7.18 (m, 2H), 6.93-6.96 (m, 2H), 5.77 (br. s, 0.6H), 4.90 (br. s, 0.4H), 4.22-4.32 (m, 1H), 3.86 (s, 3H), 3.18-3.56 (m, 4H), 2.47 (s, 3H), 1.80-2.15 (m, 4H), 1.46-1.52 (m, 9H); MS: m/z 524.2 (M+H)+.

후처리

  1. customsealed Schlenk tube
  2. customwas irradiated in a microwave reactor at 130° C. for 30 min
  3. washwashed with saturated NH4Cl(aq) and H2O
  4. washThe organic phase was washed with H2O
  5. dry with materialdried over Na2SO4
  6. filtrationThe mixture was filtered
  7. customthe filtrate was evaporated under reduced pressure
  8. customto give the crude material
  9. customThe crude material was purified by flash column chromatography (SiO2)
  10. washeluting with a heptane-EtOAc gradient

출처 및 근거

ORD 기록
ord-6d4694b59f3041c4b9ecd92a38331310
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08513271B2

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