Pyridine → HCID 178450901, compound

HRID 1486854Notes

Reaction equation

HRID 1486854 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:41])[CH2:21][C@@:22]1([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[O:26][N:25]=[C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=2)[CH2:23]1)([CH3:18])([CH3:17])[CH3:16].N1C=CC=CC=1.CC(N(C)C)=O>O>[C:15]([O:19][C:20](=[O:41])[CH2:21][C@@:22]1([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[O:26][N:25]=[C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([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:28]=2)[CH2:23]1)([CH3:17])([CH3:18])[CH3:16]

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 31374Dimethylacetamide2×HCID 131736824tert-Butyl (5S)-5-(2-tert-butoxy-2-oxoethyl)-3-(3-hydroxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylateHCID 178479379HCID 178479379, compound2×

Product 1

HCID 178450901HCID 178450901, compoundYield 56.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-Carbamimidamidobenzoyl chloride hydrochloride (2.158 g) was added to a mixture of tert-butyl (5S)-5-(2-tert-butoxy-2-oxoethyl)-3-(3-hydroxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate (1.74 g), pyridine (2.2 mL), and DMA (2.2 mL) at 50 C, and the obtained mixture was stirred at 50 C for 3 hours. Further, 4-carbamimidamidobenzoyl chloride hydrochloride (2.158 g), DMA (1.1 mL), and pyridine (1.1 mL) were added thereto, and the obtained mixture was stirred at 50 C for 2 hours. To the reaction mixture, water was added, followed by extraction with ethyl acetate and ethyl acetate/THF (1/1). The extract was washed with brine and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate, subsequently acetonitrile/acetic acid), and then, the obtained fraction was concentrated under reduced pressure. The residue was added to a saturated aqueous solution of sodium bicarbonate, 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 (1.40 g).

Workup

  1. stirringthe obtained mixture was stirred at 50 C for 2 hours
  2. extractionfollowed by extraction with ethyl acetate and ethyl acetate/THF (1/1)
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate, subsequently acetonitrile/acetic acid), and then, the obtained fraction
  7. concentrationwas concentrated under reduced pressure
  8. additionThe residue was added to a saturated aqueous solution of sodium bicarbonate
  9. extractionfollowed by extraction with ethyl acetate
  10. dry with materialThe extract was dried over anhydrous magnesium sulfate
  11. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-2ad35ab5024747568ae5321605a209b5
Source dataset
uspto-grants-2016_08
Patent number
US09428470B2

Reaction notes

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