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

HRID 129020Notes

Reaction equation

HRID 129020 reaction equation
[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]

Participants

9

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 5

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-ad0afdacb1bd44e8b4c99488789d760a
Source dataset
uspto-grants-1995_11
Patent number
US05466692

Reaction notes

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