Cyclohexylamine → (3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide

HRID 2367297노트

반응식

HRID 2367297 반응식
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[C@H:15]([CH3:16])[CH2:14][CH2:13][C@H:12]([C:17]([OH:19])=O)[CH2:11]2)[CH:3]=1.CCN(C(C)C)C(C)C.[CH:29]1([NH2:35])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[C@H:15]([CH3:16])[CH2:14][CH2:13][C@H:12]([C:17]([NH:35][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[O:19])[CH2:11]2)[CH:3]=1

참가 물질

6

반응물 4

HCID 7965CyclohexylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51356007(3S,6R)-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid

생성물 1

HCID 51357955(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide수율 108.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a suspension of (3S,6R)-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid (3.05 g, 10.71 mmol) in CH2Cl2 (50 mL) at room temperature was added Hunig's base (2.70 mL, 15.43 mmol, 1.3 equiv) and cyclohexylamine (1.60 mL, 14.2 mmol, 1.2 equiv), and the resulting mixture was chilled in an ice bath. To this stirred solution was added HATU (4.96 g, 13.1 mmol, 1.1 equiv) in one portion, and the resulting suspension was stirred in the ice bath for 30 minutes. LCMS showed conversion complete. The mixture was diluted with CH2Cl2 (50 mL) and filtered through celite. The filtrate was washed water (2×25 mL) and then brine. The organic was dried over Na2SO4, filtered, and concentrated in vacuo. Silica gel column chromatography using gradient elution of 1% EtOAc in CHCl3 to 50% EtOAc in CHCl3 afforded the title compound (4.26 g) as a foam. LC-MS (ES) m/z=366 [M+H]+.

후처리

  1. temperaturethe resulting mixture was chilled in an ice bath
  2. filtrationfiltered through celite
  3. washThe filtrate was washed water (2×25 mL)
  4. dry with materialThe organic was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washelution of 1% EtOAc in CHCl3 to 50% EtOAc in CHCl3

출처 및 근거

ORD 기록
ord-8c5c112157474633a87409aaf890c52b
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697685B2

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