Dimethylformamide → HCID 117868449, compound

HRID 627573Notes

Reaction equation

HRID 627573 reaction equation
Cl[C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:10]([Cl:18])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:19]([C:31]3[N:35]([CH3:36])[CH:34]=[N:33][CH:32]=3)([C:21]3[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=3)[OH:20])[CH:8]=2)[N:3]=1.C(O)(C(F)(F)F)=O.[NH:44]1[CH2:47][CH2:46][CH2:45]1.CN(C)C=O>C(OCC)(=O)C>[N:44]1([C:2]2[C:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[C:10]([Cl:18])[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([C:19]([C:31]4[N:35]([CH3:36])[CH:34]=[N:33][CH:32]=4)([C:21]4[CH:22]=[N:23][C:24]([C:27]([F:28])([F:30])[F:29])=[CH:25][CH:26]=4)[OH:20])[CH:8]=3)[N:3]=2)[CH2:47][CH2:46][CH2:45]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 10422AzetidineHCID 131735321HCID 131735321, compound

Product 1

HCID 117868449HCID 117868449, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a 5 mL sealed tube was added (2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)[6-(trifluoromethyl)pyridin-3-yl]methanol (200 mg, 0.38 mmol, 1 equivalent, Example 109), azetidine (108 mg, 1.89 mmol, 5 equivalents) and dimethylformamide (2 mL). The reaction vessel was sealed and heated in a 100° C. oil bath. After two days, the vessel was cooled and contents transferred to a reparatory funnel with ethyl acetate dilution. The organic phase was extracted with saturated, aqueous ammonium chloride solution and deionized water. The organic phase was separated, dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to provide racemic (2-azetidin-1-yl-4-chloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl) [6-(trifluoromethyl)pyridin-3-yl]methanol. MS (ESI): mass calcd. for C29H23ClF3N5O, 549.15. m/z found, 550.3 [M+H]+. 1H NMR (600 MHz, MeOD) δ 8.76 (d, J=2.0 Hz, 1H), 8.04-7.97 (m, 2H), 7.83 (d, J=8.2 Hz, 1H), 7.78-7.70 (m, 2H), 7.58 (dd, J=8.9, 2.2 Hz, 1H), 7.51-7.41 (m, 3H), 7.33 (d, J=7.8 Hz, 2H), 6.33 (s, 1H), 3.72-3.61 (m, 4H), 3.48 (s, 3H), 2.10-2.02 (m, 2H).

Workup

  1. customTo a 5 mL sealed tube
  2. customThe reaction vessel was sealed
  3. temperaturethe vessel was cooled
  4. extractionThe organic phase was extracted with saturated, aqueous ammonium chloride solution
  5. customThe organic phase was separated
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness under reduced pressure
  9. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-ee522a6d66bb4fdb9d4181d4449cbd9f
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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