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

HRID 926642Notes

Reaction equation

HRID 926642 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.[NH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>CN(C=O)C>[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:35])([F:36])[F:34])=[CH:31][CH:32]=3)[OH:26])[CH:8]=2)[N:3]=[C:2]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]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

4

Reactant 2

HCID 8083MorpholineHCID 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 118006233{4-Chloro-2-morpholin-4-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 6228DimethylformamideSolvent

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), morpholine (144 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 48 hours. The vessel was then cooled to room temperature and the solvent was removed by a stream of nitrogen. 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 C34H29ClF3N7O2, 659.2. m/z found, 660.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ ppm 8.80 (d, J=1.9 Hz, 1H), 8.17 (d, J=2.0 Hz, 1H), 7.88-7.83 (m, 3H), 7.63 (d, J=1.4 Hz, 1H), 7.60-7.52 (m, 3H), 7.25 (s, 1H), 7.22 (d, J=8.7 Hz, 2H), 7.10 (s, 1H), 6.42 (dd, J=2.4, 1.9 Hz, 1H), 6.21 (d, J=0.9 Hz, 1H), 4.38 (s, 2H), 3.83-3.75 (m, 4H), 3.30 (s, 3H), 3.25-3.16 (m, 4H).

Workup

  1. customsealed
  2. temperaturemaintained at that temperature for 48 hours
  3. temperatureThe vessel was then cooled to room temperature
  4. customthe solvent was removed by a stream of nitrogen
  5. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-2fc4b1996b6e41d88a4872f2b8676b76
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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