1,1-Dichloroethane → HCID 178473725, compound

HRID 849424Notes

Reaction equation

HRID 849424 reaction equation
Cl.Cl.Cl.[NH:4]1[CH:8]=[C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[CH:18][C:19]([C:21]4[CH:22]=N[CH:24]=[CH:25][CH:26]=4)=[CH:20][C:15]=3[CH2:14][N:13]([C:27](=[O:32])[C:28](F)(F)F)[CH:12]([CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:11]2)[N:6]=[CH:5]1.[CH:40](C1N=CNC=1)=O.[Cl:47]C(Cl)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(OCC)(=O)C.[OH-].[NH4+].C(O)(=O)C>[ClH:47].[C:27]([N:13]1[CH2:14][C:15]2[CH:20]=[C:19]([C:21]3[CH:22]=[CH:40][CH:24]=[CH:25][CH:26]=3)[CH:18]=[CH:17][C:16]=2[N:10]([CH2:9][C:7]2[N:6]=[CH:5][NH:4][CH:8]=2)[CH2:11][C@H:12]1[CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)(=[O:32])[CH3:28]

Participants

8

Reactant 4

HCID 63651,1-DichloroethaneHCID 764281H-Imidazole-4-carbaldehyde2×HCID 5049666Sodium triacetoxyborohydride2×HCID 178478619HCID 178478619, compound

Product 1

HCID 178473725HCID 178473725, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of Compound B (140 mg, 0.35 mmol), 4-formyl imidazole (68 mg, 0.7 mmol), dichloroethane (2 mL) and acetic acid (2 mL) was stirred at room temperature for 30 min and sodium triacetoxyborohydride (150 mg, 0.7 mmol) was added. The solution was heated to 60° C., stirred for 18 hour, and additional portions of 4-formyl imidazole and sodium triacetoxyborohydride were added (0.2 mmol each, 4 portions over 8 hours); the mixture was diluted with ethyl acetate (20 mL) and ammonium hydroxide (5 ml, conc), and stirred for an additional 30 min. The mixture was extracted with ethyl acetate (2×25 mL) and the combined organic extracts were washed with aqueous sodium bicarbonate (25 ml, saturated solution), and then ammonium chloride (25 mL, sat aqueous solution), dried (Na2SO4), and concentrated in vacuo to a semi-solid. The crude was purified by preparative HPLC (aqueous methanol gradient containing 0.1% TFA, C-18 column) and lyophilized to provide Compound C as a white solid (80 mg, 48%). MS: (M+H)+ 471

Workup

  1. stirringstirred for an additional 30 min
  2. extractionThe mixture was extracted with ethyl acetate (2×25 mL)
  3. washthe combined organic extracts were washed with aqueous sodium bicarbonate (25 ml, saturated solution)
  4. dry with materialammonium chloride (25 mL, sat aqueous solution), dried (Na2SO4)
  5. concentrationconcentrated in vacuo to a semi-solid
  6. customThe crude was purified by preparative HPLC (aqueous methanol gradient containing 0.1% TFA, C-18 column)

Sources & evidence

ORD record
ord-43be0825aa844e8db0ad28ca6da308b4
Source dataset
uspto-grants-2000_01
Patent number
US06011029

Reaction notes

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