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 220540노트

반응식

HRID 220540 반응식
[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]

참가 물질

6

반응물 4

HCID 176Acetic Acid2회HCID 712Formaldehyde2회HCID 4039589(5-Methyl-pyrazol-1-yl)-acetic acid ethyl esterHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazine

생성물 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 ester수율 16.3%

시약·촉매·용매 1

HCID 702Ethanol용매

반응 조건

온도
120 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-16c7a4812e794b56a0267696e02f7e97
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202873B2

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