Ethyl Acetate → 2-((1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclohexyl)-ethanenitrile

HRID 527077

반응식

HRID 527077 반응식
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:16][C@@:13]3([O:15][CH2:14]3)[CH2:12][CH2:11][CH2:10]2)[C:5]([F:17])=[CH:4][N:3]=1.[C-:18]#[N:19].[Na+].Cl([O-])(=O)(=O)=O.[Li+].CCOC(C)=O>CC#N>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:10][CH2:11][CH2:12][C@:13]([CH2:14][C:18]#[N:19])([OH:15])[CH2:16]2)[C:5]([F:17])=[CH:4][N:3]=1

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 8929Sodium CyanideHCID 23665649Lithium perchlorateHCID 866674522-chloro-5-fluoro-N-[(3S)-1-oxaspiro[2.5]octan-7-yl]pyrimidin-4-amine

생성물 1

HCID 866674512-((1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclohexyl)-ethanenitrile

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
100 °C

실험 절차

A suspension of 2-chloro-5-fluoro-N-[(3S)-1-oxaspiro[2.5]octan-7-yl]pyrimidin-4-amine, 49c, (0.50 g, 1.94 mmol), NaCN (0.11 g, 2.33 mmol) and lithium perchlorate (0.25 g, 2.33 mmol) in CH3CN was heated at 100° C. in a pressure tube for 3 h. The mixture was diluted into EtOAc and the organic phase was washed with aqueous saturated NaHCO3 solution, dried with MgSO4, filtered and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel chromatography (EtOAc/hexanes) afforded the desired product: 1H NMR (300.0 MHz, CDCl3) δ 7.78 (d, J=2.7 Hz, 1H), 4.85 (d, J=6.6 Hz, 1H), 4.28 (qn, J=4.0 Hz, 1H), 2.45 (s, 2H), 2.16 (d, J=13.0 Hz, 1H), 2.05 (d, J=11.7 Hz, 1H), 1.80-1.71 (m, 3H), 1.46-1.28 (m, 2H) and 1.17-1.06 (m, 1H) ppm; LCMS RT=2.15 (M+H) 285.34.

후처리

  1. washthe organic phase was washed with aqueous saturated NaHCO3 solution
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. customthe solvent was removed under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-6b319e48328843038b293b307c0f24a3
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345708B2

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