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 2359632ノート

反応式

HRID 2359632 の反応式
[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]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 22392014(5-(Methylsulfanyl)pyridin-3-yl)boronic acid2 回HCID 582430462-(S)-{[2-Chloro-4-(4-methoxy-phenoxy)-pyrimidin-5-ylamino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

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

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-d7bdbeee60ab44688b332d2a4d5c9779
出典データセット
uspto-grants-2014_04
特許番号
US08685990B2

反応ノート

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