Ethanol → HCID 57437893, compound

HRID 1799395Notes

Reaction equation

HRID 1799395 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][CH2:14][CH3:15])=[C:11]([C:16]([NH:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:17])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.O1C[CH2:38][O:37][CH2:36][CH2:35]1.C([OH:42])C>CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd].CN(C1C=CN=CC=1)C.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[CH:19]1([NH:18][C:16]([C:11]2[CH:10]=[N:9][N:8]([C:5]3[CH:6]=[CH:7][C:2]([C:38]([O:37][CH2:36][CH3:35])=[O:42])=[CH:3][CH:4]=3)[C:12]=2[CH2:13][CH2:14][CH3:15])=[O:17])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

8

Reactant 4

HCID 702EthanolHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 2808093HCID 2808093, compound2×

Product 1

HCID 57437893HCID 57437893, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Conditions

Temperature
150 °C

Procedure

1-(4-chlorophenyl)-N-cyclohexyl-5-propyl-pyrazole-4-carboxamide (Intermediate #22) (159 mg, 0.46 mmol), Molybdenum hexacarbonyl (61 mg, 0.23 mmol), Herrmann's catalyst (Trans-Di-Mu-Acetatobis[2-(Di-O-Tolylphosphino)Benzyl]dipalladium(II), 22 mg, 0.02 mmol), DMAP (113 mg, 0.92 mmol), DIPEA (161 μL, 0.92 mmol), Fu's salt (Tri-(T-Butyl)Phosphonium Hydrogen tetrafluoroborate Salt, 27 mg, 0.09 mmol), Dioxane (2 mL), Ethanol (2 L) were mixed into a microwave tube. The reaction mixture was then heated at 150° C. for 1 hour by microwave. LC-MS showed complete conversion to the product. The solvent was evaporated under reduced pressure and the reaction mixture extracted with EtOAc (2×25 mL), washed with water (10 mL), 2N HCl (10 mL) and brine (10 mL). The organic phase was dried over MgSO4 and evaporated under reduced pressure to give a black gum. The residue was purified by column chromatography (12 g silicycle column, gradient: 1:0 to 1:1 hexane/EtOAc) and appropriate fractions combined and concentrated in vacuo to yield the desired compound as a white solid (130 mg, 74%).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. extractionthe reaction mixture extracted with EtOAc (2×25 mL)
  3. washwashed with water (10 mL), 2N HCl (10 mL) and brine (10 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. customevaporated under reduced pressure
  6. customto give a black gum
  7. customThe residue was purified by column chromatography (12 g silicycle column, gradient: 1:0 to 1:1 hexane/EtOAc) and appropriate fractions
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-15923e7c529842848d18b5a344bd54a9
Source dataset
uspto-grants-2013_01
Patent number
US08344016B2

Reaction notes

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