Dimethylformamide → tert-butyl 6-amino-7-(cyclohexylethynyl)-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(methyl)carbamate

HRID 2387719Notes

Reaction equation

HRID 2387719 reaction equation
[C:1]([O:5][C:6](=[O:21])[N:7]([C:9]1[C:14]2[N:15]=[CH:16][N:17]([CH3:18])[C:13]=2[C:12](I)=[C:11]([NH2:20])[N:10]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[C:22]([CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)#[CH:23].C(NC(C)C)(C)C.CN(C)C=O>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[NH2:20][C:11]1[N:10]=[C:9]([N:7]([CH3:8])[C:6](=[O:21])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:14]2[N:15]=[CH:16][N:17]([CH3:18])[C:13]=2[C:12]=1[C:23]#[C:22][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 70263Ethynylcyclohexane2×HCID 46894439tert-Butyl (6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)(methyl)carbamate

Product 1

HCID 60133861tert-butyl 6-amino-7-(cyclohexylethynyl)-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(methyl)carbamate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A1.12 tert-Butyl-6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(methyl)carbamate (1.0 g, 2.48 mmol), dichlorobis(triphenylphosphine)palladium (75 mg, 0.11 mmol), ethynylcyclohexane (0.3 g, 2.8 mmol), CuI (25 mg, 0.13 mmol), and diisopropylamine (5 mL) were added to N,N-dimethylformamide (7 mL). The reaction mixture was heated at 95° C. (in preheated oil bath) for 60 min. Additional ethynylcyclohexane (0.3 g, 2.8 mmol) was added to the reaction mixture and heated for another 60 min. The reaction was cooled and diluted with ethyl acetate and washed several times with water. The solvent removed under reduced pressure and the residue was chromatographed on a silica gel column (50%-70% ethyl acetate/hexane) to give 400 mg of C32.1 as a yellow solid. LCMS B: Ret time 3.15 min, (M+H)+=384.41.

Workup

  1. temperatureheated for another 60 min
  2. temperatureThe reaction was cooled
  3. washwashed several times with water
  4. customThe solvent removed under reduced pressure
  5. customthe residue was chromatographed on a silica gel column (50%-70% ethyl acetate/hexane)
  6. customto give 400 mg of C32.1 as a yellow solid
  7. customRet time 3.15 min, (M+H)+=384.41

Sources & evidence

ORD record
ord-8476e8040a9443f9b77fb4635d97a440
Source dataset
uspto-grants-2012_09
Patent number
US08268855B2

Reaction notes

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