Isopropanol → HCID 178434473, compound

HRID 419744Notes

Reaction equation

HRID 419744 reaction equation
Cl.Cl.[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[N:13]([CH3:15])[CH:14]=2)=[CH:6][C:5]=1[C:22]([F:25])([F:24])[F:23].Cl[C:27]1[C:32]([C:33](=O)[CH3:34])=[C:31](Cl)[N:30]=[CH:29][N:28]=1.C(O)(C)C.O.[NH2:42][NH2:43]>C(Cl)Cl.CO>[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]([CH:16]3[CH2:21][CH2:20][N:19]([C:31]4[N:30]=[CH:29][N:28]=[C:27]5[NH:42][N:43]=[C:33]([CH3:34])[C:32]=45)[CH2:18][CH2:17]3)[N:13]([CH3:15])[CH:14]=2)=[CH:6][C:5]=1[C:22]([F:23])([F:24])[F:25]

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 24654Hydrazine hydrate (1:1)HCID 122782591-(4,6-Dichloro-5-pyrimidinyl)ethanoneHCID 866320204-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidine dihydrochloride salt

Product 1

HCID 178434473HCID 178434473, compoundYield 50.29%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

In a microwave vial charge 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidine dihydrochloride salt (0.5 g, 1.0 eq), 1-(4,6-dichloro-pyrimidin-5-yl)-ethanone (0.22 g, 1.0 eq), TEA (1.2 mL, 8.0 eq) and isopropyl alcohol (5 mL). Stirr the reaction mass at 80° C. for 45 min in microwave. Monitor the reaction by TLC (10% MeOH in DCM). Cool the reaction mass to 0° C. and add hydrazine hydrate (0.07 mL, 1.2 eq). Slowly bring the reaction mass to RT. Stirr the reaction mass at 80° C. for 45 min in microwave. Monitor the reaction by TLC (10% MeOH in DCM). Concentrate the reaction mass under vacuum. Charge ethyl acetate and then wash with water and saturated aq. sodium chloride. Dry the organic layer over anhydrous Na2SO4 and concentrate it under reduced pressure. Purify the compound by column chromatography (Silica gel 60-120 mesh, DCM-Methanol). Crystallize the product in diethyl ether and filter it to give 4-(4-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazol-2-yl)piperidin-1-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine (0.254 g, 50.29%). MS (M+H): m/z=460.5

Workup

  1. customto RT
  2. customat 80° C.
  3. customfor 45 min
  4. concentrationConcentrate the reaction mass under vacuum
  5. washCharge ethyl acetate and then wash with water and saturated aq. sodium chloride
  6. dry with materialDry the organic layer over anhydrous Na2SO4
  7. concentrationconcentrate it under reduced pressure
  8. customPurify the compound by column chromatography (Silica gel 60-120 mesh, DCM-Methanol)
  9. customCrystallize the product in diethyl ether
  10. filtrationfilter it

Sources & evidence

ORD record
ord-9606017a26c5431b848a9f680287c126
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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