Dimethylformamide → HCID 178491185, compound

HRID 1913563Notes

Reaction equation

HRID 1913563 reaction equation
[C:1]([O:5][C:6](=[O:49])[NH:7][CH:8]([C:21](=[O:48])[N:22]([CH:34]([C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2Br)[N:40]=1)[CH3:35])[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=1)[CH2:9][C:10]1[C:15]([CH3:16])=[CH:14][C:13]([C:17](=[O:19])[NH2:18])=[CH:12][C:11]=1[CH3:20])([CH3:4])([CH3:3])[CH3:2].[CH3:50][N:51](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6](=[O:49])[NH:7][CH:8]([C:21](=[O:48])[N:22]([CH:34]([C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:50]#[N:51])[N:40]=1)[CH3:35])[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=1)[CH2:9][C:10]1[C:15]([CH3:16])=[CH:14][C:13]([C:17](=[O:19])[NH2:18])=[CH:12][C:11]=1[CH3:20])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 178491184HCID 178491184, compound

Product 1

HCID 178491185HCID 178491185, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

To a solution of [1-[{1-[4-(2-bromo-phenyl)-1H-imidazol-2-yl]-ethyl}-(3,4-dimethoxy-benzyl)-carbamoyl]-2-(4-carbamoyl-2,6-dimethyl-phenyl)-ethyl]-carbamic acid tert-butyl ester (294 mg; 0.4 mmol) in DMF (2 mL) was added Zn(CN)2 (28 mg; 0.24 mmol). The resulting mixture was degassed with Argon for 5 min, then Pd(PPh3)4 (92 mg; 0.08 mmol) was added neat, and the system was immediately warmed to 100° C. After heating for 6 h, the reaction was cooled to rt and partitioned between EtOAc and water. The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was subjected to reverse phase HPLC (water/acetonitrile/0.1% TFA). The fractions of interest were combined, basified with saturated aqueous NaHCO3 and extracted twice with EtOAc. The EtOAc extracts were combined, dried over Na2SO4, filtered, and concentrated to afford 146 mg (54%) of desired {2-(4-carbamoyl-2,6-dimethyl-phenyl)-1-[{1-[4-(2-cyano-phenyl)-1H-imidazol-2-yl]-ethyl}-(3,4-dimethoxy-benzyl)-carbamoyl]-ethyl}-carbamic acid tert-butyl ester (HPLC: 96% @ 254 nm and 97% @ 214 nm). This sample was of sufficient quality to use in the next reaction without further purification.

Workup

  1. customThe resulting mixture was degassed with Argon for 5 min
  2. temperatureAfter heating for 6 h
  3. temperaturethe reaction was cooled to rt
  4. custompartitioned between EtOAc and water
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. extractionextracted twice with EtOAc
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-b038b310eeee41aaa0c2dfae6d3136a7
Source dataset
uspto-grants-2013_12
Patent number
US08609709B2

Reaction notes

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