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

HRID 2426391Notes

Reaction equation

HRID 2426391 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:24]=[CH:23][O:22][CH:21]=3)=[CH:16][CH:15]=2)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:25])[N:3]=1.B([C:29]1[CH:40]=[CH:39][C:32]([CH2:33][C@@H:34]([C:36]([OH:38])=[O:37])[NH2:35])=[CH:31][CH:30]=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>[NH2:35][C@@H:34]([CH2:33][C:32]1[CH:39]=[CH:40][C:29]([C:2]2[CH:7]=[C:6]([O:8][CH:9]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:24]=[CH:23][O:22][CH:21]=4)=[CH:16][CH:15]=3)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:25])[N:3]=2)=[CH:30][CH:31]=1)[C:36]([OH:38])=[O:37]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 150315L-p-BoronophenylalanineHCID 866210864-Chloro-6-[2,2,2-trifluoro-1-(4-furan-3-yl-phenyl)-ethoxy]-pyrimidin-2-ylamine

Product 1

HCID 25024711(S)-2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(4-furan-3-yl-phenyl)-ethoxy]-pyrimidin-4-yl}-phenyl)-propionic acidYield 17.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

In a microwave vial, 4-chloro-6-[2,2,2-trifluoro-1-(4-furan-3-yl-phenyl)-ethoxy]-pyrimidin-2-ylamine (30 mg, 0.081 mmol), 4-borono-L-phenylalanine (20 mg, 0.098 mmol), 1 ml of actonitrile and 0.7 ml of water were mixed. Then, 0.3 ml of 1N aqueous sodium carbonate was added to the mixture, 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 7.2 mg of (S)-2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(4-furan-3-yl-phenyl)-ethoxy]-pyrimidin-4-yl}-phenyl)-propionic acid. 1H NMR (400 MHz, CD3OD) δ (ppm) 7.96(m, 3H), 7.61(m, 5H), 6.81(s,1H), 6.77(d, J=6.8 Hz, 1H), 6.74(d, J=4.8 Hz, 1H), 4.27(q, J=5.6 Hz, 1H), 3.36(m, 1H), 3.21(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-b283793b34af4ff28e1252eac2ab376e
Source dataset
uspto-grants-2011_06
Patent number
US07968559B2

Reaction notes

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