Sodium Carbonate → Methyl[2,6-dimethyl-4-[(2'-(1-tert-butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl)amino]pyrimidin-5-yl]ketone

HRID 129020노트

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HRID 129020 반응식
[CH3:1][C:2]([C:4]1[C:5]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)=[N:6][C:7]([CH3:11])=[N:8][C:9]=1[CH3:10])=[O:3].[C:21]([N:25]1[C:29]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2B(O)O)=[N:28][N:27]=[N:26]1)([CH3:24])([CH3:23])[CH3:22].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.CCO.CCOC(C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][C:2]([C:4]1[C:5]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[C:29]3[N:25]([C:21]([CH3:24])([CH3:23])[CH3:22])[N:26]=[N:27][N:28]=3)=[CH:16][CH:15]=2)=[N:6][C:7]([CH3:11])=[N:8][C:9]=1[CH3:10])=[O:3]

참가 물질

9

반응물 3

HCID 10340Sodium CarbonateHCID 10688121Methyl(4-(4-bromobenzylamino)-2,6-dimethylpyrimidin-5-yl)ketoneHCID 109447112-[(1-tert-Butyl)-1H-tetrazol-5-yl]phenylboronic acid

생성물 1

HCID 11080952Methyl[2,6-dimethyl-4-[(2'-(1-tert-butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl)amino]pyrimidin-5-yl]ketone수율 75.1%

시약·촉매·용매 5

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 702Ethanol용매HCID 962Water용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

실험 절차

To a heated solution of methyl(4-(4-bromobenzylamino)-2,6-dimethylpyrimidin-5-yl)ketone (1.67 g, 5.00 mmol) and tetrakis(triphenylphosphine) palladium(0) (0.29 g, 0.25 mmol) in toluene (20 mL) was added a partial solution of 2-[(1-tert-butyl)-1H-tetrazol-5-yl]phenylboronic acid (1.50 g, 6.10 mmol) (prepared according to J. W. Ellingboe, et al. U.S. Pat. No. 5,149,699) and Na2CO3 (1.06 g, 10.00 mmol) in water (10 mL) and EtOH (5 mL) in several portions over 1 h. Heating was continued for 2.5 h. The mixture was diluted with EtOAc and the layers were separated. The organic phase was washed with 0.1N NaOH, brine, dried MgSO4) and concentrated. Purification by flash chromatography (40-50% EtOAc/hexane) and trituration with hexane gave 1.71 g (75% ) of product as a white solid. An analytical sample was recrystallized from ether, mp 131°-132° C.

후처리

  1. customprepared
  2. temperatureHeating
  3. customthe layers were separated
  4. washThe organic phase was washed with 0.1N NaOH, brine, dried MgSO4) and
  5. concentrationconcentrated
  6. customPurification by flash chromatography (40-50% EtOAc/hexane) and trituration with hexane

출처 및 근거

ORD 기록
ord-ad0afdacb1bd44e8b4c99488789d760a
출처 데이터셋
uspto-grants-1995_11
특허 번호
US05466692

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