Acetic Acid → {4-[3'-(4-Fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-ylmethyl]-5-methyl-pyrazol-1-yl}-acetic acid ethyl ester

HRID 220540ノート

反応式

HRID 220540 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)=[N:10][CH:11]=[CH:12][N:13]=2)=[CH:4][CH:3]=1.[CH2:20]([O:22][C:23](=[O:31])[CH2:24][N:25]1[C:29]([CH3:30])=[CH:28][CH:27]=[N:26]1)[CH3:21].[C:32](O)(=O)C.C=O>C(O)C>[CH2:20]([O:22][C:23](=[O:31])[CH2:24][N:25]1[C:29]([CH3:30])=[C:28]([CH2:32][N:17]2[CH2:16][CH2:15][N:14]([C:9]3[C:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[N:13][CH:12]=[CH:11][N:10]=3)[CH2:19][CH2:18]2)[CH:27]=[N:26]1)[CH3:21]

参加物

6

反応物 4

HCID 176Acetic Acid2 回HCID 712Formaldehyde2 回HCID 4039589(5-Methyl-pyrazol-1-yl)-acetic acid ethyl esterHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazine

生成物 1

HCID 68594551{4-[3'-(4-Fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-ylmethyl]-5-methyl-pyrazol-1-yl}-acetic acid ethyl ester収率 16.3%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
120 °C

実験手順

Combine 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.500 g, 1.94 mmol) with (5-methyl-pyrazol-1-yl)-acetic acid ethyl ester (0.416 g, 2.48 mmol) in ethanol (8 mL). Add acetic acid (801 μL, 14 mmol) and a 37% aqueous solution of formaldehyde (401 μL). Heat in microwave at 120° C. for 5 hr. Add acetic acid (801 μL, 14 mmol) and a 37% aqueous solution of formaldehyde (401 μL). Heat in microwave at 120° C. for 3 hr. Concentrate, add ethyl acetate and saturated aqueous sodium bicarbonate solution. Separate organic layer. Extract aqueous layer twice with ethyl acetate, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes then 10:90 methanol:ethyl acetate) to give {4-[3′-(4-fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-ylmethyl]-5-methyl-pyrazol-1-yl}-acetic acid ethyl ester (139 mg, 16%). MS (ES): m/z=439 [M+H]+.

後処理

  1. temperatureHeat in microwave at 120° C. for 3 hr
  2. concentrationConcentrate
  3. additionadd ethyl acetate and saturated aqueous sodium bicarbonate solution
  4. dry with materialExtract aqueous layer twice with ethyl acetate, dry (magnesium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate
  7. custompurify (silica gel chromatography
  8. washeluting with 50:50 to 100:0 ethyl acetate

出典と根拠

ORDレコード
ord-16c7a4812e794b56a0267696e02f7e97
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

反応ノート

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