Dicyclohexylcarbodiimide → HCID 178495118, compound

HRID 2065786Notes

Reaction equation

HRID 2065786 reaction equation
[N:1]([C@@H:4]([CH3:9])[CH2:5][CH2:6][O:7][CH3:8])=[C:2]=S.[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:18]2[N:19]=[C:20]([C:31]([CH3:37])([CH3:36])[C:32]([O:34][CH3:35])=[O:33])[NH:21][C:22]=2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=2[F:30])=[N:15][C:16]=1[OH:17].C1(N=C=NC2CCCCC2)CCCCC1>C(O)C>[F:30][C:24]1[CH:25]=[C:26]([F:29])[CH:27]=[CH:28][C:23]=1[C:22]1[NH:21][C:20]([C:31]([CH3:37])([CH3:36])[C:32]([O:34][CH3:35])=[O:33])=[N:19][C:18]=1[C:14]1[N:15]=[C:16]2[O:17][C:2]([NH:1][C@@H:4]([CH3:9])[CH2:5][CH2:6][O:7][CH3:8])=[N:10][C:11]2=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 86666178HCID 86666178, compoundHCID 178500115HCID 178500115, compound

Product 1

HCID 178495118HCID 178495118, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

(3S)-3-Isothiocyanato-1-methoxy-butane (24.68 g, 169.94 mmol) is added to a suspension of methyl 2-[4-(5-amino-6-hydroxy-2-pyridyl)-5-(2,4-difluorophenyl)-1H-imidazol-2-yl]-2-methyl-propanoate (55 g, 141.62 mmol) in ethanol (550 mL) at RT. The reaction mixture is stirred under reflux overnight and then cooled to 50° C. Dicyclohexylcarbodiimide (37.99 g, 184.10 mmol) is added to the mixture and the resulting suspension is stirred under reflux for 20 h. The reaction is allowed to reach RT and the solvent evaporated under reduced pressure. The residue is absorbed in silica gel and purified through a silica gel column (first using dichloromethane as an eluent to remove the most apolar impurities and then with dichloromethane/methanol 95:5 to elute the desired product) to afford the title compound (52 g, 74%) as a dark brown foam. LC-ES/MS m/z 500 (M+1).

Workup

  1. temperatureunder reflux overnight
  2. stirringthe resulting suspension is stirred
  3. temperatureunder reflux for 20 h
  4. customto reach RT
  5. customthe solvent evaporated under reduced pressure
  6. customThe residue is absorbed in silica gel
  7. custompurified through a silica gel column (
  8. customto remove the most apolar impurities
  9. washwith dichloromethane/methanol 95:5 to elute the desired product)

Sources & evidence

ORD record
ord-18651d9111054d03b68e2e500b1a2227
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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