1,2-Dichloroethane → Methyl 4-(4-(tert-butoxycarbonylamino)-1-methyl-1H-imidazole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylate

HRID 2405707Notes

Reaction equation

HRID 2405707 reaction equation
C(OC([NH:8][C:9]1[N:10]=[C:11]([C:15]([O:17][CH3:18])=[O:16])[N:12]([CH3:14])[CH:13]=1)=O)(C)(C)C.Cl.[C:20]([O:24][C:25]([NH:27][C:28]1[N:29]=[C:30]([C:34]([OH:36])=O)[N:31]([CH3:33])[CH:32]=1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(Cl)CCl.CCN(C(C)C)C(C)C>C(O)C.C1(C)C=CC=CC=1.CC(N(C)C)=O>[C:20]([O:24][C:25]([NH:27][C:28]1[N:29]=[C:30]([C:34]([NH:8][C:9]2[N:10]=[C:11]([C:15]([O:17][CH3:18])=[O:16])[N:12]([CH3:14])[CH:13]=2)=[O:36])[N:31]([CH3:33])[CH:32]=1)=[O:26])([CH3:21])([CH3:22])[CH3:23]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27572264-[(tert-Butoxycarbonyl)amino]-1-methyl-1H-imidazole-2-carboxylic acidHCID 11379828METHYL 4-(TERT-BUTOXYCARBONYLAMINO)-1-METHYL-1H-IMIDAZOLE-2-CARBOXYLATE

Product 1

HCID 59440227Methyl 4-(4-(tert-butoxycarbonylamino)-1-methyl-1H-imidazole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylateYield 71.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 31374DimethylacetamideSolvent

Procedure

Methyl 4-(tert-butoxycarbonylamino)-1-methyl-1H-imidazole-2-carboxylate (2.50 g, 9.80 mmol) in 30 ml of EtAc was added 6 ml of HCl (conc.). After stirred for 30 min, the mixture was diluted with ethanol and toluene, concentrated and co-evaporated with ethanol/toluene (1:1, 3×50 ml) to dryness compound without further purification. To the dryness compound was added 4-(tert-butoxycarbonylamino)-1-methyl-1H-imidazole-2-carboxylic acid (2.36 g, 9.8 mmol), EDC (5.90 g, 30.7 mmol), DIPEA (1.70 ml, 9.8 mmol) and 80 ml of DMA. The mixture was stirred under Ar overnight, concentrated, diluted with THF/EtAc (1:2, 150 ml), and washed 1M NaH2PO4/NaCl (conc) and NaHCO3 (conc) separately. The organic solvent layer was separated and dried over MgSO4, filtered, concentrated and purified on SiO2 chromatography eluted with EtAc/DCM (1:25 to 1:15) to afford 2.65 g (71.5%) of the title product. 1H NMR (DMSO) 11.17 (s, 1H), 10.48 (s, 1H), 7.58 (s, 1H), 7.32 (s, 1H), 4.01 (s, 3H), 3.94 (s, 3H), 3.92 (s, 3H), 1.45 (s, 9H); 13C NMR 160.60, 157.30, 135.92, 135.45, 132.86, 126.12, 114.83, 79.50, 52.70, 35.58, 34.92, 28.08; MS m/z+ 401.8 (M+Na).

Workup

  1. concentrationconcentrated and co-evaporated with ethanol/toluene (1:1, 3×50 ml) to dryness compound without further purification
  2. stirringThe mixture was stirred under Ar overnight
  3. concentrationconcentrated
  4. additiondiluted with THF/EtAc (1:2, 150 ml)
  5. washwashed 1M NaH2PO4/NaCl (conc) and NaHCO3 (conc) separately
  6. customThe organic solvent layer was separated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified on SiO2 chromatography
  11. washeluted with EtAc/DCM (1:25 to 1:15)

Sources & evidence

ORD record
ord-031f01fd0d1a400bb356ccb464b8afe5
Source dataset
uspto-grants-2014_08
Patent number
US08809320B2

Reaction notes

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