Dimethylformamide → {4-Chloro-2-(3-fluoroazetidin-1-yl)-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(1-methyl-1H-imidazol-5-yl)[6-(trifluoromethyl)pyridin-3-yl]methanol

HRID 926643Notes

Reaction equation

HRID 926643 reaction equation
Cl[C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][CH:14]=2)=[C:10]([Cl:24])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:25]([C:37]3[N:41]([CH3:42])[CH:40]=[N:39][CH:38]=3)([C:27]3[CH:28]=[N:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=3)[OH:26])[CH:8]=2)[N:3]=1.Cl.[F:44][CH:45]1[CH2:48][NH:47][CH2:46]1.CN(C=O)C>CCOC(C)=O>[Cl:24][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:25]([C:37]3[N:41]([CH3:42])[CH:40]=[N:39][CH:38]=3)([C:27]3[CH:28]=[N:29][C:30]([C:33]([F:34])([F:35])[F:36])=[CH:31][CH:32]=3)[OH:26])[CH:8]=2)[N:3]=[C:2]([N:47]2[CH2:48][CH:45]([F:44])[CH2:46]2)[C:11]=1[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH:23]=[CH:22][CH:21]=[N:20]2)=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 101250543-fluoroazetidine HydrochlorideHCID 74221463(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloroquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol2×

Product 1

HCID 118006273{4-Chloro-2-(3-fluoroazetidin-1-yl)-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(1-methyl-1H-imidazol-5-yl)[6-(trifluoromethyl)pyridin-3-yl]methanol

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

{2,4-Dichloro-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(1-methyl-1H-imidazol-5-yl)pyrimidin-2-ylmethanol (100 mg, 0.164 mmol, Intermediate 65), 3-fluoroazetidine hydrochloride (183 mg, 1.64 mmol) and DMF (2 mL) were combined in a reaction tube, then sealed and heated to 100° C. and maintained at that temperature for 24 hours. The residue was taken up into EtOAc, transferred to a reparatory funnel and extracted twice with a saturated, aqueous NH4Cl solution. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to afford the title compound. MS (ESI): mass calcd. for C33H26ClF4N7O, 647.2. m/z found, 648.2 [M+H]+. 1H NMR (600 MHz, CDCl3) δ ppm 8.82 (d, J=1.7 Hz, 1H), 8.09 (d, J=2.0 Hz, 1H), 7.97-7.93 (m, 1H), 7.86 (d, J=2.3 Hz, 1H), 7.76 (d, J=8.8 Hz, 1H), 7.67 (d, J=1.5 Hz, 1H), 7.64 (d, J=8.3 Hz, 1H), 7.59 (d, J=8.6 Hz, 2H), 7.55-7.51 (m, 1H), 7.26 (s, 1H), 7.16 (d, J=8.6 Hz, 2H), 6.46-6.42 (m, 1H), 6.39 (s, 1H), 4.41-4.31 (m, 2H), 4.29 (s, 2H), 4.27-4.18 (m, 3H), 3.44 (s, 3H).

Workup

  1. customsealed
  2. temperaturemaintained at that temperature for 24 hours
  3. customtransferred to a reparatory funnel
  4. extractionextracted twice with a saturated, aqueous NH4Cl solution
  5. customThe organic phase was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-c7c1979eb4fd457ab85763517d33725d
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

Loading…