Phosgene → HCID 54079200, compound

HRID 1068408Notes

Reaction equation

HRID 1068408 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:19])[C:5]1([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.[C:20](Cl)(Cl)=[O:21].C(N(CC)CC)C.Cl.[C:32]([C:34]1[CH:46]=[CH:45][C:37]([CH2:38][N:39]2[C:43]([NH2:44])=[CH:42][N:41]=[CH:40]2)=[CH:36][CH:35]=1)#[N:33]>C1(C)C=CC=CC=1.C(Cl)Cl>[CH3:2][O:3][C:4](=[O:19])[C:5]1([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[CH2:6][CH2:7][N:8]([C:20]([NH:44][C:43]2[N:39]([CH2:38][C:37]3[CH:45]=[CH:46][C:34]([C:32]#[N:33])=[CH:35][CH:36]=3)[CH:40]=[N:41][CH:42]=2)=[O:21])[CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 21193372HCID 21193372, compoundHCID 21193404HCID 21193404, compound

Product 1

HCID 54079200HCID 54079200, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-(2-methylbenzyl)-isonipecotic acid methyl ester hydrochloride (50 mg, 0.176 mmol) in toluene (2 ml) was added phosgene (0.912 ml of a 1.93M solution in toluene, 1.76 mmol) and triethylamine (0.074 ml, 0.528 mmol) and the mixture stirred for 48 hrs at room temperature. The excess phosgene was removed by purging the solution with argon gas for 10 min. The suspension was added to 1-(4-cyanobenzyl)-5-amino-1H-imidazole hydrochloride (100 mg, 0.528 mmol) in CH2Cl2 (10 ml) and the mixture stirred at 50° C. for 72 hrs. The solvent was evaporated in vacuo and the residue purified by preparative HPLC (C18, 95:5 to 5:95 water: acetonitrile containing 0.1% TFA). The residue after lyophilisation was partitioned between CH2Cl2 and saturated NaHCO3 solution. The organic extract was dried (MgSO4), and evaporated to dryness

Workup

  1. customThe excess phosgene was removed
  2. customby purging the solution with argon gas for 10 min
  3. stirringthe mixture stirred at 50° C. for 72 hrs
  4. customThe solvent was evaporated in vacuo
  5. customthe residue purified by preparative HPLC (C18, 95:5 to 5:95 water: acetonitrile containing 0.1% TFA)
  6. customThe residue after lyophilisation was partitioned between CH2Cl2 and saturated NaHCO3 solution
  7. extractionThe organic extract
  8. dry with materialwas dried (MgSO4)
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-337abbf1197c447dabb05a660af953a6
Source dataset
uspto-grants-2001_06
Patent number
US06248756B1

Reaction notes

Loading…