Acetonitrile → 2-Amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-trifluoromethylphenyl)-ethoxy]-pyrimidin-4-yl}-phenyl)-propionic acid

HRID 2239931Notes

Reaction equation

HRID 2239931 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([F:23])([F:22])[F:21])[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:24])[N:3]=1.B([C:28]1[CH:39]=[CH:38][C:31]([CH2:32][C@@H:33]([C:35]([OH:37])=[O:36])[NH2:34])=[CH:30][CH:29]=1)(O)O.C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:34][CH:33]([CH2:32][C:31]1[CH:38]=[CH:39][C:28]([C:2]2[CH:7]=[C:6]([O:8][CH:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]([F:23])([F:22])[F:21])[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:24])[N:3]=2)=[CH:29][CH:30]=1)[C:35]([OH:37])=[O:36]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 150315L-p-BoronophenylalanineHCID 866142934-Chloro-2-amino-6-[1-(2-trifluoromethylphenyl)-2,2,2-trifluoro-ethoxy]-pyrimidine

Product 1

HCID 740736982-Amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-trifluoromethylphenyl)-ethoxy]-pyrimidin-4-yl}-phenyl)-propionic acidYield 11.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

In a microwave vial, 4-chloro-2-amino-6-[1-(2-trifluoromethylphenyl)-2,2,2-trifluoro-ethoxy]-pyrimidine (33 mg, 0.1 mmol), 4-borono-L-phenylalanine (31 mg, 0.15 mmol) and 1 ml of acetonitrile, 0.7 ml of water. 0.3 ml of 1N aqueous sodium carbonate was added to above solution followed by 5 mole percent of dichlorobis(triphenylphosphine)-palladium(II). The reaction vessel was sealed and heated at 150° C. for 5 minutes with microwave irradiation. After cooling, the reaction mixture was evaporated to dryness. The residue was dissolved in 2.5 ml of methanol, and then was purified by Prep-LC to give 5.6 mg of 2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-trifluoromethylphenyl)-ethoxy]-pyrimidin-4-yl}-phenyl)-propionic acid. 1H NMR (400 MHz, CD3OD) δ 7.96 (m, 3H), 7.80 (d, J=8.06 Hz, 1H), 7.74 (t, J=7.91 Hz 1H), 7.63 (t, J=8.06 Hz, 1H), 7.41 (d, J=8.3 Hz, 2H), 7.21 (m, 1H), 6.69 (s, 1H), 3.87 (m, 1H), 3.34 (m, 1H), 3.08 (m, 1H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureAfter cooling
  3. customthe reaction mixture was evaporated to dryness
  4. dissolutionThe residue was dissolved in 2.5 ml of methanol
  5. customwas purified by Prep-LC

Sources & evidence

ORD record
ord-d0b28c35dd3a42eebc8b1e03f928a769
Source dataset
uspto-grants-2010_05
Patent number
US07723345B2

Reaction notes

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