Hydrochloric Acid → [4-(3-Pyrimidylcarboxyamino)-2-phenylbenzoyl]methionine methyl ester

HRID 383126Notes

Reaction equation

HRID 383126 reaction equation
C[O:2][C:3](N1C=CC=NC1)=[O:4].[OH-].[Na+].Cl.Cl.[CH3:15][O:16][C:17](=[O:39])[C@H:18]([CH2:35][CH2:36][S:37][CH3:38])[NH:19][C:20](=[O:34])[C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][C:22]=1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.ON1C(=O)C2C=CC=CC=2N=N1.CN(C)CC[CH2:56][N:57]=[C:58]=[N:59][CH2:60][CH3:61].C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C>[CH3:15][O:16][C:17](=[O:39])[C@H:18]([CH2:35][CH2:36][S:37][CH3:38])[NH:19][C:20](=[O:34])[C:21]1[CH:26]=[CH:25][C:24]([N:27]([N:57]2[CH:56]=[CH:61][CH:60]=[N:59][CH2:58]2)[C:3]([OH:4])=[O:2])=[CH:23][C:22]=1[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 69612387(4-Amino-2-phenylbenzoyl)methionine methyl ester hydrochloride2×HCID 702124973-Pyrimidinecarboxylic acid methyl ester

Product 1

HCID 69845184[4-(3-Pyrimidylcarboxyamino)-2-phenylbenzoyl]methionine methyl esterYield 41%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of the 5-pyrimidinecarboxylic acid methyl ester prepared in Example 219A (682 mg, 4.94 mmol) and aqueous sodium hydroxide solution (4.0 M, 2.5 mL) in THF was heated at 60° C. for 1.5 hours. Hydrochloric acid (6.0 N, 2 mL) was added to the reaction mixture, and the solvent was evaporated in vacuo. The residue was dried under high vacuum at 50° C. for 1 hour, and the redesolved in to THF. To the acid solution was added (4-amino-2-phenylbenzoyl)methionine methyl ester (compound 8, 1.97 g, 5.0 mmol), 3-hydroxy 1,2,3-benzotriazin-4(3H)-one (0.978 g, 6.0 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.15 g, 6.0 mmol) and triethylamine (2.8 mL, 20 mmol). After 14 hours, the reaction mixture was diluted with ethyl acetate (100 mL), washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was then purified by column chromatography (50% ethyl acetate-hexane, then ethyl acetate) to give [4-(3-pyrimidylcarboxyamino)-2-phenylbenzoyl]methionine methyl ester (0.937 g, 41%).

Workup

  1. customthe solvent was evaporated in vacuo
  2. customThe residue was dried under high vacuum at 50° C. for 1 hour
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was then purified by column chromatography (50% ethyl acetate-hexane

Sources & evidence

ORD record
ord-5ffb306a633444b48646a6b11235b4b1
Source dataset
uspto-grants-2001_10
Patent number
US06310095B1

Reaction notes

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