Valine methyl ester → HCID 66738463, compound

HRID 1641850Notes

Reaction equation

HRID 1641850 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]2[N:21]=[C:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[O:23][C:24]=2[C:25]([F:28])([F:27])[F:26])=[O:19])=[CH:13][N:12]=1)[C:5](O)=[O:6].[CH3:35][O:36][C:37](=[O:43])[C@@H:38]([NH2:42])[CH:39]([CH3:41])[CH3:40].ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>ClCCl>[CH3:35][O:36][C:37](=[O:43])[CH:38]([NH:42][C:5](=[O:6])[C:4]1[CH:8]=[CH:9][C:10]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[N:21]=[C:22]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[O:23][C:24]=3[C:25]([F:27])([F:26])[F:28])=[O:19])=[CH:13][N:12]=2)=[C:2]([Cl:1])[CH:3]=1)[CH:39]([CH3:41])[CH3:40]

Participants

6

Reactant 4

HCID 94285Valine methyl esterHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57652100HCID 57652100, compound

Product 1

HCID 66738463HCID 66738463, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-chloro-4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoic acid (50 mg, 0.1 mmol), (S)-2-amino-3-methyl-butyric acid methyl ester (17 mg, 0.1 mmol), 1-hydroxy-7-azabenzotriazole (HOAT) (21 mg, 0.15 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (30 mg, 0.15 mmol) in anhydrous dichloromethane (3 mL) was stirred at room temperature for 3 h. The reaction mixture was concentrated and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried and concentrated to give a solid. The solid was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, 0%-100% ethyl acetate in hexane) to give 2-(3-chloro-4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoylamino)-3-methyl-butyric acid methyl ester (41 mg, 66%) as a white solid. LCMS calcd for C29H24ClF3N4O5 (m/e) 600, obsd 601 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customto give a solid
  7. customThe solid was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, 0%-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ae1bb4cb39284901b4c698c5ee4f5b20
Source dataset
uspto-grants-2012_02
Patent number
US08115011B2

Reaction notes

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