Pyridine → HCID 178450897, compound

HRID 1486901Notes

Reaction equation

HRID 1486901 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].[O:15]=[S:16]1(=[O:54])[CH2:21][CH2:20][N:19]([C:22](=[O:53])[CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][C:26]=2[C:32]2[CH2:36][C:35]([CH2:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[O:34][N:33]=2)[CH2:18][CH2:17]1.N1C=CC=CC=1.CN1C(=O)CCC1>C(#N)C>[NH:2]([C:6]1[CH:14]=[CH:13][C:9]([C:10]([O:31][C:28]2[CH:29]=[CH:30][C:25]([CH2:24][CH2:23][C:22]([N:19]3[CH2:18][CH2:17][S:16](=[O:15])(=[O:54])[CH2:21][CH2:20]3)=[O:53])=[C:26]([C:32]3[CH2:36][C:35]([CH2:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([CH2:37][C:38](=[O:39])[O:40][C:41]([CH3:44])([CH3:42])[CH3:43])[O:34][N:33]=3)[CH:27]=2)=[O:11])=[CH:8][CH:7]=1)[C:3]([NH2:5])=[NH:4]

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 13387N-methyl-2-pyrrolidone2×HCID 118292770HCID 118292770, compoundHCID 178479379HCID 178479379, compound6×

Product 1

HCID 178450897HCID 178450897, compoundYield 27.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-Carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was added to a mixture of di-tert-butyl 2,2′-(3-(2-(3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropyl)-5-hydroxyphenyl)-4,5-dihydro-1,2-oxazole-5,5-diyl)diacetate (140 mg), pyridine (0.2 mL), and NMP (0.2 mL) at 50 C, and the obtained mixture was stirred at 50 C for 30 minutes. 4-Carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was further added thereto, and the obtained mixture was stirred at 50 C for 30 minutes. 4-Carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was further added thereto, and the obtained mixture was stirred at 50 C for 3 hours. Pyridine (0.2 mL) and NMP (0.2 mL) were further added thereto, 4-carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was added thereto, and then, the obtained mixture was stirred at 50 C for 30 minutes. 4-Carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was further added thereto, and the obtained mixture was stirred at 50 C for 30 minutes. 4-carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was further added thereto, and the obtained mixture was stirred overnight at 50 C. To the reaction mixture, acetonitrile was added. The precipitate was filtered off, and then, the filtrate was concentrated under reduced pressure. The residue was 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 (49.0 mg).

Workup

  1. stirringthe obtained mixture was stirred at 50 C for 30 minutes
  2. stirringthe obtained mixture was stirred at 50 C for 3 hours
  3. stirringthe obtained mixture was stirred at 50 C for 30 minutes
  4. stirringthe obtained mixture was stirred at 50 C for 30 minutes
  5. stirringthe obtained mixture was stirred overnight at 50 C
  6. filtrationThe precipitate was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. additionTo the obtained fraction, a saturated aqueous solution of sodium bicarbonate was added
  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-95e94d59ef714bd3a8371d0fec07bb04
Source dataset
uspto-grants-2016_08
Patent number
US09428470B2

Reaction notes

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