N,N-二甲基甲酰胺 → 6-[(1E)-2-[4-(4-氟苯基)-6-异丙基-2-[甲基(甲磺酰)氨基]-5-嘧啶]乙烯基]-2,2-二甲基-1,3-二氧六环-4-乙酸叔丁酯

HRID 1663307笔记

反应方程式

HRID 1663307 反应方程式
Br[C:2]1[C:3]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[N:4][C:5]([N:11]([CH3:16])[S:12]([CH3:15])(=[O:14])=[O:13])=[N:6][C:7]=1[CH:8]([CH3:10])[CH3:9].[CH3:24][C:25]1([CH3:41])[O:30][C@@H:29]([CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][C@@H:27]([CH:39]=[CH2:40])[O:26]1.C1(CNCC2CCCCC2)CCCCC1.CN(C)C=O>C(OCC)(=O)C.O.C(O)(=O)C>[F:23][C:20]1[CH:21]=[CH:22][C:17]([C:3]2[C:2](/[CH:40]=[CH:39]/[C@H:27]3[O:26][C:25]([CH3:24])([CH3:41])[O:30][C@@H:29]([CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28]3)=[C:7]([CH:8]([CH3:10])[CH3:9])[N:6]=[C:5]([N:11]([CH3:16])[S:12]([CH3:15])(=[O:14])=[O:13])[N:4]=2)=[CH:18][CH:19]=1

参与物

8

反应物 4

HCID 6228N,N-二甲基甲酰胺HCID 4594378Bis(cyclohexylmethyl)amineHCID 11495059N-(5-Bromo-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideHCID 67371871tert-butyl 2-((4R,6S)-2,2-dimethyl-6-vinyl-1,3-dioxan-4-yl)acetate

产物 1

HCID 99162186-[(1E)-2-[4-(4-氟苯基)-6-异丙基-2-[甲基(甲磺酰)氨基]-5-嘧啶]乙烯基]-2,2-二甲基-1,3-二氧六环-4-乙酸叔丁酯

试剂、催化剂与溶剂 3

HCID 176醋酸溶剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂2 次HCID 8857乙酸乙酯溶剂2 次

反应条件

温度
50 °C

实验过程

A mixture of N-(5-bromo-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (1.00 g, 2.50 mmol), bis-tri-tert-butylphosphine palladium (0) (131 mg, 0.250 mmol), tert-butyl 2-((4R,6S)-2,2-dimethyl-6-vinyl-1,3-dioxan-4-yl)acetate (640 mg, 2.50 mmol), water (5 mL), N,N-dicyclohexylmethylamine (0.530 mL, 2.50 mmol), and N,N-dimethylformamide (5 mL) was heated and stirred at 50° C. under nitrogen for four days. The mixture was then diluted with ethyl acetate (11 mL), water (10 mL), and acetic acid (0.2 mL). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (5 mL). The combined organic phases were washed with water (10 mL), then brine (10 mL), and concentrated in vacuo to give a yellow oil containing some solids. This material was adsorbed onto silica gel through dissolution in ethyl acetate, then purified by flash chromatography (5% ethyl acetate in isohexane gradually increasing to 20% ethyl acetate in hexane, silica column 25 mm in diameter and 250 mm in height) to yield tert-butyl 2-((4R,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethanesulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate of the formula

后处理

  1. temperaturewas heated
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (5 mL)
  4. washThe combined organic phases were washed with water (10 mL)
  5. concentrationbrine (10 mL), and concentrated in vacuo
  6. customto give a yellow oil
  7. additioncontaining some solids
  8. custompurified by flash chromatography (5% ethyl acetate in isohexane
  9. temperaturegradually increasing to 20% ethyl acetate in hexane, silica column 25 mm in diameter and 250 mm in height)

来源与证据

ORD记录
ord-b4ef65ee28e84db0a8587c4fe9643027
来源数据集
uspto-grants-2011_10
专利号
US08034932B2

反应笔记

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