tert-Butyl piperazine-1-carboxylate → 4-[1-(3-Fluoro-benzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydro-quinazolin-5-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 901867노트

반응식

HRID 901867 반응식
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][N:5]([CH3:21])[C:6](=[O:20])[N:7]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1.[C:22]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:25]([O:24][C:22]([N:29]1[CH2:34][CH2:33][N:32]([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH2:4][N:5]([CH3:21])[C:6](=[O:20])[N:7]3[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)[CH2:31][CH2:30]1)=[O:23])([CH3:28])([CH3:26])[CH3:27]

참가 물질

7

반응물 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-2회HCID 184445195-bromo-1-(3-fluoro-benzyl)-3-methyl-3,4-dihydro-1H-quinazolin-2-oneHCID 23676156Sodium t-butoxide

생성물 1

HCID 691151024-[1-(3-Fluoro-benzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydro-quinazolin-5-yl]-piperazine-1-carboxylic acid tert-butyl ester수율 35.2%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

실험 절차

A solution of 5-bromo-1-(3-fluoro-benzyl)-3-methyl-3,4-dihydro-1H-quinazolin-2-one (156 mg, 0.45 mmol) and 1-Boc-piperazine (100 mg, 0.54 mmol) in 1 ml toluene was added to a mixture of Pd2(dba)3 (8 mg, 0.009 mmol), BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (14 mg, 0.022 mmol), and NaOt-Bu (65 mg, 0.67 mmol). With stirring, the solution was heated at 95° C.-100° C. for 1 hour and was allowed to cool to room temperature. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was washed with water and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by prep TLC to give 72 mg 4-[1-(3-fluoro-benzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydro-quinazolin-5-yl]-piperazine-1-carboxylic acid tert-butyl ester as yellow solid (75 mg, 35%).

후처리

  1. temperaturethe solution was heated at 95° C.-100° C. for 1 hour
  2. filtrationThe reaction mixture was filtered through celite
  3. washwashed with ethyl acetate
  4. washThe filtrate was washed with water and brine
  5. dry with materialAfter drying over MgSO4
  6. concentrationthe organic fraction was concentrated in vacuo
  7. customresulting brown residue
  8. customwas purified by prep TLC

출처 및 근거

ORD 기록
ord-33d245776f8a4bf8aa469671fa78f767
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07365063B2

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