Dimethylformamide → tert-butyl 6-amino-7-((3-cyano-5-fluorophenyl)ethynyl)-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(methyl)carbamate

HRID 2387718Notes

Reaction equation

HRID 2387718 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]([C:24]1[CH:25]=[C:26]([CH:29]=[C:30]([F:32])[CH:31]=1)[C:27]#[N:28])#[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][C:24]1[CH:31]=[C:30]([F:32])[CH:29]=[C:26]([C:27]#[N:28])[CH:25]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 167365813-Ethynyl-5-fluorobenzonitrile2×HCID 46894439tert-Butyl (6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)(methyl)carbamate

Product 1

HCID 67526848tert-butyl 6-amino-7-((3-cyano-5-fluorophenyl)ethynyl)-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
90 °C

Procedure

A1.12 tert-Butyl-6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(methyl)carbamate (3.2 g, 7.9 mmol), dichlorobis(triphenylphosphine)palladium (270 mg, 0.38 mmol), 3-ethynyl-5-fluorobenzonitrile (C1.2) (1.5 g, 10 mmol), CuI (75 mg, 0.39 mmol), diisopropylamine (15 mL) were added to N,N-dimethylformamide (15 mL). The reaction mixture was heated at 90° C. (in preheated oil bath) for 60 min. Additional 3-ethynyl-5-fluorobenzonitrile (C1.2) (0.5 g, 3.4 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 purified by silica gel column chromatography (50%-70% ethyl acetate/hexane) to give 3.0 g (90%) of C1.3. LCMS B: Ret time 2.98 min, (M+H)+=421.31, 1H NMR, 400 MHz, CDCl3: 7.62 (s, 1H), 7.57 (s, 1H), 7.42 (dm, 1H), 7.35 (dm, 1H), 5.00 (bs, 2H), 4.05 (s, 3H), 3.39 (s, 3H), 1.44 (s, 9H).

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 purified by silica gel column chromatography (50%-70% ethyl acetate/hexane)
  6. customto give 3.0 g (90%) of C1.3
  7. customRet time 2.98 min, (M+H)+=421.31, 1H NMR, 400 MHz, CDCl3: 7.62 (s, 1H), 7.57 (s, 1H), 7.42 (dm, 1H), 7.35 (dm, 1H), 5.00 (bs, 2H), 4.05 (s, 3H), 3.39 (s, 3H), 1.44 (s, 9H)

Sources & evidence

ORD record
ord-9f413e74352a437caedf87c2bd7d1d8c
Source dataset
uspto-grants-2012_09
Patent number
US08268855B2

Reaction notes

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