Water → 2-Amino-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester

HRID 230326Notes

Reaction equation

HRID 230326 reaction equation
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:37])[CH:11]([NH:29]C(OC(C)(C)C)=O)[CH2:12][CH:13]=[CH:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]([CH3:28])[C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[CH:17][CH:16]=1.O.C(=O)([O-])O.[Na+]>ClCCl>[CH3:8][O:9][C:10](=[O:37])[CH:11]([NH2:29])[CH2:12][CH:13]=[CH:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]([CH3:28])[C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 669119472-Tert-butoxycarbonylamino-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester

Product 1

HCID 669119952-Amino-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl esterYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under an argon atmosphere, palladium acetate (54 mg) and tris(2-methylphenyl)phosphine (70 mg) were added to a suspension of N-Boc-allylglycine methyl ester (1.03 g), N-(4-iodophenyl)-N-methylpyrimidin-2-amine (1.40 g) and potassium carbonate (933 mg) in DMF (15 ml), and the resulting mixture was stirred at 80° C. overnight. The reaction solution was allowed to cool to room temperature and ethyl acetate was added thereto. The solution was washed 3 times with water and once with saturated brine, and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was purified by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=20/1-4/1). The obtained solid was recrystallized from hexane/ethyl acetate mixed solvent to obtain 2-tert-butoxycarbonylamino-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (976 mg). (4) Trifluoroacetic acid (2 ml) was added to a solution of 2-tert-butoxycarbonylamino-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (976 mg) in dichloromethane (20 ml), and the resulting mixture was stirred at room temperature for 4.5 hours. Water was added to the reaction solution, and sodium hydrogen carbonate was added thereto in small portions to neutralize it, followed by extracting the resulting solution twice with chloroform. Organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated to dryness to obtain 2-amino-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (599 mg). NMR (HL, CDCl3): δ 2.58-2.64 (2H, brm), 3.48-3.58 (1H, brm), 3.52 (3H, s), 3.75 (3H, s), 6.07-6.14 (1H, m), 6.49 (1H, d, J=5.6 Hz), 6.57 (1H, t, J=4.6 Hz), 7.26 (2H, d, J=8.1 Hz), 7.38 (2H, d, J=8.3 Hz), 8.34 (2H, d, J=4.6 Hz)

Workup

  1. additionwas added
  2. extractionby extracting the resulting solution twice with chloroform
  3. washOrganic layers were washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customAfter removing anhydrous sodium sulfate
  6. filtrationby filtration
  7. concentrationthe filtrate was concentrated to dryness

Sources & evidence

ORD record
ord-b6110f3b7c594a2399e87f525169ecc7
Source dataset
uspto-grants-2009_07
Patent number
US07566724B2

Reaction notes

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