Methanol → HCID 57829790, compound

HRID 1855492Notes

Reaction equation

HRID 1855492 reaction equation
[CH2:1]([C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[C:10](Cl)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[NH2:49][C:50]1[CH:55]=[CH:54][C:53]([N:56]2[CH:60]=[C:59]([CH2:61][OH:62])[N:58]=[CH:57]2)=[CH:52][CH:51]=1>O1CCOCC1.CN(C)C(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH:49][C:50]2[CH:51]=[CH:52][C:53]([N:56]3[CH:60]=[C:59]([CH2:61][OH:62])[N:58]=[CH:57]3)=[CH:54][CH:55]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 887MethanolHCID 11430Potassium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 13399964HCID 13399964, compoundHCID 866336184-Benzyl-2-chloro-6-methyl-pyrimidine

Product 1

HCID 57829790HCID 57829790, compoundYield 26.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of 4-benzyl-2-chloro-6-methyl-pyrimidine (86 mg, 0.39 mmol), 1-(4-amino-phenyl)-1H-imidazol-4-yl]-methanol (75 mg, 0.39 mmol, Europ. J. Med. Chem. 19 (3), 285-7 (1984), CAS 94128-93-5) and potassium carbonate (1.10 g, 7.86 mmol) in dioxane (4 mL) and N,N-dimethylacetamide (1 mL) was degassed with nitrogen. Palladium(II) acetate (3.6 mg, 0.016 mmol) and 2-(dicyclohexylphosphino)biphenyl (12 mg, 0.031 mmol) were added and the reaction mixture was irradiated in a microwave oven at 200° C. for 25 minutes. [1-(4-Amino-phenyl)-1H-imidazol-4-yl]-methanol (43 mg, 0.19 mmol) was added and the reaction mixture was irradiated in a microwave oven at 200° C. for another 25 minutes. The reaction mixture was filtered; the filtrate was diluted with ethyl acetate, washed with water and brine, dried with magnesium sulfate and concentrated in vacuo. Purification by column chromatography on silica eluting with dichloromethane/methanol (14:1 v/v) afforded the title compound as a light yellow viscous oil (19 mg, 13%). MS ISP (m/e): 372.2 [(M+H)+].

Workup

  1. customwas degassed with nitrogen
  2. customthe reaction mixture was irradiated in a microwave oven at 200° C. for 25 minutes
  3. customthe reaction mixture was irradiated in a microwave oven at 200° C. for another 25 minutes
  4. filtrationThe reaction mixture was filtered
  5. additionthe filtrate was diluted with ethyl acetate
  6. washwashed with water and brine
  7. dry with materialdried with magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography on silica eluting with dichloromethane/methanol (14:1 v/v)

Sources & evidence

ORD record
ord-978d7ca715d540cc8565d081b9eafa38
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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