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

HRID 527077

反応式

HRID 527077 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-6b319e48328843038b293b307c0f24a3
出典データセット
uspto-grants-2016_05
特許番号
US09345708B2

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