1,4-Dioxane → (R)-4-((1-cyclobutylethyl)amino)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

HRID 81085Notes

Reaction equation

HRID 81085 reaction equation
Br[C:2]1[C:3]2[N:19]=[CH:18][N:17]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=3)[C:4]=2[C:5]([NH:10][C@@H:11]([CH:13]2[CH2:16][CH2:15][CH2:14]2)[CH3:12])=[N:6][C:7]=1[C:8]#[N:9].[CH3:31]B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(Cl)(Cl)Cl.O>[CH:13]1([C@H:11]([NH:10][C:5]2[C:4]3[N:17]([CH2:20][C:21]4[CH:22]=[CH:23][C:24]([C:27]([F:28])([F:30])[F:29])=[CH:25][CH:26]=4)[CH:18]=[N:19][C:3]=3[C:2]([CH3:31])=[C:7]([C:8]#[N:9])[N:6]=2)[CH3:12])[CH2:16][CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 139377Methylboronic AcidHCID 86724462(R)-7-bromo-4-((1-cyclobutylethyl)amino)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Product 1

HCID 86724464(R)-4-((1-cyclobutylethyl)amino)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Reagents, catalysts & solvents 2

HCID 178478479HCID 178478479, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a vial containing (R)-7-bromo-4-((1-cyclobutylethyl)amino)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (65 mg, 0.14 mmol), methylboronic acid (16.3 mg, 0.3 mmol), 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride-chloroform adduct (11.1 mg, 0.014 mmol) and potassium phosphate (87 mg, 0.41 mmol) was added 1,4-dioxane (800 ul) and water (200 uL). The vial was evacuated and refilled with Ar (3×). The solution was heated to 120° C. for 10 minutes under microwave irradiation. The mixture was cooled to room temperature and quenched with saturated sodium bicarbonate and ethyl acetate. The organic layer was collected and concentrated. The residue was dissolved in DCM and purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to give (R)-4-((1-cyclobutylethyl)amino)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C22H22F3N5 [M+H]+ 414. found 414.

Workup

  1. customThe vial was evacuated
  2. additionrefilled with Ar (3×)
  3. temperatureThe mixture was cooled to room temperature
  4. customquenched with saturated sodium bicarbonate and ethyl acetate
  5. customThe organic layer was collected
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in DCM
  8. custompurified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-a1586bdcb20648ee806593c7c75ae80d
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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