Dimethylformamide → HCID 74221331, compound

HRID 928861Notes

Reaction equation

HRID 928861 reaction equation
Cl[C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[C:10]([Cl:23])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:24]([C:36]3[N:40]([CH3:41])[CH:39]=[N:38][CH:37]=3)([C:26]3[CH:27]=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=3)[OH:25])[CH:8]=2)[N:3]=1.[NH:42]1[CH2:45][CH2:44][CH2:43]1.CN(C)C=O>C(OCC)(=O)C>[N:42]1([C:2]2[C:11]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:20])([F:21])[F:22])=[CH:15][CH:14]=3)=[C:10]([Cl:23])[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([C:24]([C:36]4[N:40]([CH3:41])[CH:39]=[N:38][CH:37]=4)([C:26]4[CH:27]=[N:28][C:29]([C:32]([F:33])([F:34])[F:35])=[CH:30][CH:31]=4)[OH:25])[CH:8]=3)[N:3]=2)[CH2:45][CH2:44][CH2:43]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 10422AzetidineHCID 86715674HCID 86715674, compound2×

Product 1

HCID 74221331HCID 74221331, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a 75 mL sealed tube was added (2,4-dichloro-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (2.50 g, 4.09 mmol, intermediate 60), azetidine (0.83 mL, 12.3 mmol) and dimethylformamide (30 mL). The reaction vessel was sealed and heated in a 100° C. oil bath. After overnight heating, the vessel was cooled and contents transferred to a separatory funnel with ethyl acetate dilution. The organic phase was extracted with a 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. Chromatography on silica gel (dichloromethane increasing to 10% ((2M ammonia in methanol) in dichloromethane)) provided the title compound. MS (ESI): mass calcd. for C31H24ClF6N5O, 631.16; m/z found, 632.5 [M+H]+. 1H NMR (600 MHz, Chloroform-d) δ 8.81 (d, J=2.2 Hz, 1H), 8.05 (d, J=2.1 Hz, 1H), 7.87 (dd, J=8.3, 2.2 Hz, 1H), 7.70 (d, J=8.8 Hz, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.52 (d, J=8.0 Hz, 2H), 7.46 (dd, J=8.8, 2.2 Hz, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.09 (d, J=1.1 Hz, 1H), 6.19 (d, J=1.1 Hz, 1H), 4.32 (s, 2H), 4.13 (t, J=7.7 Hz, 4H), 3.31 (s, 3H), 2.29-2.20 (m, 2H).

Workup

  1. customTo a 75 mL sealed tube
  2. customThe reaction vessel was sealed
  3. temperatureAfter overnight heating
  4. temperaturethe vessel was cooled
  5. extractionThe organic phase was extracted with a saturated, aqueous ammonium chloride solution
  6. customThe organic phase was separated
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-7759bfbd762146e89a02937aa5a1888d
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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