1,8-Diazabicyclo(5.4.0)undec-7-ene → (R)-6-chloro-N-(1-cyclobutylethyl)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridin-4-amine

HRID 1852687Notes

Reaction equation

HRID 1852687 reaction equation
[F-].[K+].Cl[C:4]1[C:9]2[N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:11]=[N:12][C:8]=2[CH:7]=[C:6]([Cl:24])[N:5]=1.Cl.[CH:26]1([C@H:30]([NH2:32])[CH3:31])[CH2:29][CH2:28][CH2:27]1.C1CCN2C(=NCCC2)CC1>CC(N(C)C)=O.O.CCOC(C)=O>[Cl:24][C:6]1[N:5]=[C:4]([NH:32][C@@H:30]([CH:26]2[CH2:29][CH2:28][CH2:27]2)[CH3:31])[C:9]2[N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:11]=[N:12][C:8]=2[CH:7]=1

Participants

8

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 522689Potassium FluorideHCID 69658276(1R)-1-cyclobutylethan-1-amine hydrochlorideHCID 867244584,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine

Product 1

HCID 86724459(R)-6-chloro-N-(1-cyclobutylethyl)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridin-4-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

Potassium fluoride (0.940 g, 16.18 mmol) was added to a stirred solution of 4,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine (2.8 g, 8.09 mmol) in DMA (22.40 ml). The solution was stirred at room temperature for 5 min. (R)-1-cyclobutylethanamine hydrochloride (2.194 g, 16.18 mmol) and DBU (3.66 ml, 24.27 mmol) were added and the reaction mixture was heated at 120° C. overnight. The reaction mixture was cooled to room temperature and diluted with water and EtOAc. The aqueous layer was extracted with EtOAc (2×). The organic layers were combined, dried and concentrated. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford (R)-6-chloro-N-(1-cyclobutylethyl)-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridin-4-amine. MS ESI calc'd for C20H20ClF3N4 [M+H]+ 409. found 409.

Workup

  1. additionwere added
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionThe aqueous layer was extracted with EtOAc (2×)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-035525d001ab4ceea7b9b6dc4eff7a6d
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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