Dimethylacetamide → (1s,2r,4r)-n-[2-(4-Cyano-benzenesulfonylmethyl)-4-(isopropyl-methyl-amino)-cyclohexyl]-2-(4-trifluoromethyl-1h-benzoimidazol-2-yl)-acetamide

HRID 641581Notes

Reaction equation

HRID 641581 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C@@H:12]2[CH2:17][C@H:16]([N:18]([CH:20]([CH3:22])[CH3:21])[CH3:19])[CH2:15][CH2:14][C@@H:13]2[NH:23][C:24](=[O:39])[CH2:25][C:26]2[NH:30][C:29]3[CH:31]=[CH:32][CH:33]=[C:34]([C:35]([F:38])([F:37])[F:36])[C:28]=3[N:27]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C[C:41]([N:43](C)C)=O>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[Zn]>[C:41]([C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH2:11][C@@H:12]2[CH2:17][C@H:16]([N:18]([CH:20]([CH3:21])[CH3:22])[CH3:19])[CH2:15][CH2:14][C@@H:13]2[NH:23][C:24](=[O:39])[CH2:25][C:26]2[NH:30][C:29]3[CH:31]=[CH:32][CH:33]=[C:34]([C:35]([F:36])([F:37])[F:38])[C:28]=3[N:27]=2)(=[O:10])=[O:9])=[CH:6][CH:7]=1)#[N:43]

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 11192943(1S,2R,4R)-N-[2-(4-Bromo-benzenesulfonylmethyl)-4-(isopropyl-methyl-amino)-cyclohexyl]-2-(4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetamide

Product 1

HCID 11753466(1s,2r,4r)-n-[2-(4-Cyano-benzenesulfonylmethyl)-4-(isopropyl-methyl-amino)-cyclohexyl]-2-(4-trifluoromethyl-1h-benzoimidazol-2-yl)-acetamide

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
105 °C

Procedure

(1S,2R,4R)-N-[2-(4-Bromo-benzenesulfonylmethyl)-4-(isopropyl-methyl-amino)-cyclohexyl]-2-(4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetamide, Example 3, (30 mg) was dissolved in DMA (1 ml) prior to the addition of Zn(CN)2 (34 mg), Pd2(dba)3 (10 mg), dppf (11 mg) and Zn powder (4 mg). The resulting solution was heated at 105° C. oil bath for over night. After cooling, the solution was concentrated. EtOAc and 10% amminum hydroxide (aq) were added. The organic layer was dried, filtered, and concentrated. Reverse phase HPLC purification (gradient elution, water/acetonitrile/TFA) of the resulting residue provided the title compound (8 mg). MS found: (M+H)+=576.5.

Workup

  1. temperatureAfter cooling
  2. concentrationthe solution was concentrated
  3. additionEtOAc and 10% amminum hydroxide (aq) were added
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customReverse phase HPLC purification (gradient elution, water/acetonitrile/TFA) of the resulting residue

Sources & evidence

ORD record
ord-a0e1d878ab1942c2ba56edc83b3bcda0
Source dataset
uspto-grants-2010_04
Patent number
US07696205B2

Reaction notes

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