1-Butanol → (R)-ethyl 5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1631302ノート

反応式

HRID 1631302 の反応式
Cl[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:4]2[N:3]=1.Cl.Cl.[F:18][C:19]1[CH:20]=[C:21]([C@H:27]2[CH2:31][CH2:30][CH2:29][NH:28]2)[C:22]([O:25][CH3:26])=[N:23][CH:24]=1.C(N(C(C)C)CC)(C)C.C(O)CCC>CCOC(C)=O>[F:18][C:19]1[CH:20]=[C:21]([C@H:27]2[CH2:31][CH2:30][CH2:29][N:28]2[C:2]2[CH:7]=[CH:6][N:5]3[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:4]3[N:3]=2)[C:22]([O:25][CH3:26])=[N:23][CH:24]=1

参加物

6

反応物 4

HCID 2631-ButanolHCID 81531DiisopropylethylamineHCID 58063474Ethyl 5-chloropyrazolo(1,5-a)pyrimidine-3-carboxylateHCID 66847679(R)-5-fluoro-2-methoxy-3-(pyrrolidin-2-yl)pyridine dihydrochloride

生成物 1

HCID 86664565(R)-ethyl 5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate収率 56.3%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

Ethyl 5-chloropyrazolo[1,5-a]pyrimidine-3-carboxylate (Preparation B, 0.75 g, 3.32 mmol), (R)-5-fluoro-2-methoxy-3-(pyrrolidin-2-yl)pyridine dihydrochloride (0.984 g, 3.66 mmol), diisopropylethylamine (2.32 mL, 13.3 mmol) and n-butanol (1.11 mL) were heated at 90° C. for 48 hours. The reaction mixture was diluted with EtOAc and the mixture was washed with water, brine and saturated NaHCO3. The organic layer was dried with MgSO4, filtered and concentrated afford a dark orange oil. The oil was purified by silica chromatography, eluting with a 50-80% EtOAc/Hexane gradient, to afford (R)-ethyl 5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (0.72 g, 56.2%) as a yellow foam. MS (apci) m/z=386.0 (M+H).

後処理

  1. washthe mixture was washed with water, brine and saturated NaHCO3
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customafford a dark orange oil
  6. customThe oil was purified by silica chromatography
  7. washeluting with a 50-80% EtOAc/Hexane gradient

出典と根拠

ORDレコード
ord-17847951198f46e493b30f28472380b7
出典データセット
uspto-grants-2014_07
特許番号
US08791123B2

反応ノート

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