Pyridine → tert-Butyl 5-(2-tert-butoxy-2-oxoethyl)-3-(5-((4-carbamimidamidobenzoyl)oxy)-2-methylphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate

HRID 1486850Notes

Reaction equation

HRID 1486850 reaction equation
Cl.[NH:2]([C:6]1[CH:14]=[CH:13][C:9]([C:10](Cl)=[O:11])=[CH:8][CH:7]=1)[C:3]([NH2:5])=[NH:4].[C:15]([O:19][C:20](=[O:42])[CH2:21][C:22]1([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[O:26][N:25]=[C:24]([C:27]2[CH:32]=[C:31]([OH:33])[CH:30]=[CH:29][C:28]=2[CH3:34])[CH2:23]1)([CH3:18])([CH3:17])[CH3:16].N1C=CC=CC=1>CN1C(=O)CCC1>[C:15]([O:19][C:20](=[O:42])[CH2:21][C:22]1([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[O:26][N:25]=[C:24]([C:27]2[CH:32]=[C:31]([O:33][C:10](=[O:11])[C:9]3[CH:8]=[CH:7][C:6]([NH:2][C:3]([NH2:5])=[NH:4])=[CH:14][CH:13]=3)[CH:30]=[CH:29][C:28]=2[CH3:34])[CH2:23]1)([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 1049PyridineHCID 118292827tert-Butyl 5-(2-tert-butoxy-2-oxoethyl)-3-(5-hydroxy-2-methylphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylateHCID 178479379HCID 178479379, compound4×

Product 1

HCID 178426884tert-Butyl 5-(2-tert-butoxy-2-oxoethyl)-3-(5-((4-carbamimidamidobenzoyl)oxy)-2-methylphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylateYield 51.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-Carbamimidamidobenzoyl chloride hydrochloride (173 mg) was added to a mixture of tert-butyl 5-(2-tert-butoxy-2-oxoethyl)-3-(5-hydroxy-2-methylphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate (290 mg), pyridine (1 mL), and NMP (3 mL) at 50 C, and the obtained mixture was stirred at 50 C for 20 minutes. Further, 4-carbamimidamidobenzoyl chloride hydrochloride (173 mg) was added thereto, and the obtained mixture was stirred at 50 C for 20 minutes. Further, 4-carbamimidamidobenzoyl chloride hydrochloride (173 mg) was added thereto, and the obtained mixture was stirred at 50 C for 3 hours. Further, 4-carbamimidamidobenzoyl chloride hydrochloride (173 mg) was added thereto, and the obtained mixture was stirred overnight at 50 C. The reaction mixture was purified by silica gel column chromatography (NH, ethyl acetate/hexane, subsequently methanol/ethyl acetate) and then further fractionated by HPLC (C18, mobile phase: water/acetonitrile (system containing 0.1% TFA)). To the obtained fraction, a saturated aqueous solution of sodium bicarbonate was added, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain the title compound (210 mg).

Workup

  1. stirringthe obtained mixture was stirred at 50 C for 20 minutes
  2. stirringthe obtained mixture was stirred at 50 C for 3 hours
  3. stirringthe obtained mixture was stirred overnight at 50 C
  4. customThe reaction mixture was purified by silica gel column chromatography (NH, ethyl acetate/hexane, subsequently methanol/ethyl acetate) and
  5. additionTo the obtained fraction, a saturated aqueous solution of sodium bicarbonate was added
  6. extractionfollowed by extraction with ethyl acetate
  7. dry with materialThe extract was dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-77e03750c5714f008dcd50f4ca8bbb63
Source dataset
uspto-grants-2016_08
Patent number
US09428470B2

Reaction notes

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