1,2-Dichloroethane → HCID 178473725, compound

HRID 849402Notes

Reaction equation

HRID 849402 reaction equation
N[C:2]1[CH:32]=[CH:31][C:5]2[CH2:6][N:7](C(OC(C)(C)C)=O)[CH:8]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:9][N:10]([CH2:11][C:12]3[N:13]=[CH:14][NH:15][CH:16]=3)[C:4]=2[CH:3]=1.[CH:33]([C:35]1N=CN[CH:39]=1)=O.C(O[BH-](O[C:50](=[O:52])[CH3:51])OC(=O)C)(=O)C.[Na+].[C:54]([O-])(O)=O.[Na+].[OH-].[NH4+].[Cl:61][CH2:62][CH2:63]Cl>C(O)(=O)C>[ClH:61].[C:50]([N:7]1[CH2:6][C:5]2[CH:31]=[C:32]([C:35]3[CH:39]=[CH:63][CH:62]=[CH:54][CH:33]=3)[CH:2]=[CH:3][C:4]=2[N:10]([CH2:11][C:12]2[N:13]=[CH:14][NH:15][CH:16]=2)[CH2:9][C@H:8]1[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)(=[O:52])[CH3:51]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 764281H-Imidazole-4-carbaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 178451486HCID 178451486, compound

Product 1

HCID 178473725HCID 178473725, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Compound E (5.0 g, 14.0 mmol) and 4-formylimidazole (4.45 g, 46.3 mmol) were dissolved in 1,2-DCE (100 mL) and acetic acid (50 mL). Sodium triacetoxyborohydride (4.45 g, 21.0 mmol) was added all at once and the mixture was stirred at room temperature for 1 h. Saturated NaHCO3 (50 mL) was added followed by ammonium hydroxide (50 mL). The mixture was stirred for 2 h, concentrated and the residue was partitioned between water (100 mL) and ethyl acetate (200 mL). The organic layer was washed with water (100 mL), brine (100 mL), dried (Na2SO4), concentrated and chromatographed (silica gel, 5.1×15 cm, 95% dichloromethane, 5% methanol) to yield the free base of Example 225 as a brown solid (4.9 g). This brown solid was further purified by preparative HPLC (YMC S-15 ODS column, 50×500 mm; solvent A, 0.1% TFA in 90% water, 10% methanol; solvent B, 0.1% TFA in 10% water, 90% methanol: 20-100% B in 60 min, flow rate 25 mL/min). Fractions containing the desired product were combined, concentrated and lyophilized. This lyophilate was dissolved in acetonitrile (50 mL) and 1N HCl (50 mL). This mixture was concentrated and lyophilized. This procedure is repeated to provide Example 226 as a yellow solid (2.3 g, 35%)

Workup

  1. stirringThe mixture was stirred for 2 h
  2. concentrationconcentrated
  3. customthe residue was partitioned between water (100 mL) and ethyl acetate (200 mL)
  4. washThe organic layer was washed with water (100 mL), brine (100 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customchromatographed (silica gel, 5.1×15 cm, 95% dichloromethane, 5% methanol)

Sources & evidence

ORD record
ord-8fafd9ba53b441f28e0841baac9e3a60
Source dataset
uspto-grants-2000_01
Patent number
US06011029

Reaction notes

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