Dimethylformamide → {2-Azetidin-1-yl-4-chloro-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926640Notes

Reaction equation

HRID 926640 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:33]3[C:34]([CH3:40])=[N:35][C:36]([CH3:39])=[CH:37][CH:38]=3)([C:27]3[N:31]([CH3:32])[N:30]=[N:29][CH:28]=3)[OH:26])[CH:8]=2)[N:3]=1.[NH:41]1[CH2:44][CH2:43][CH2:42]1.CN(C=O)C>CCOC(C)=O>[N:41]1([C:2]2[C:11]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)=[C:10]([Cl:24])[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([C:25]([C:33]4[C:34]([CH3:40])=[N:35][C:36]([CH3:39])=[CH:37][CH:38]=4)([C:27]4[N:31]([CH3:32])[N:30]=[N:29][CH:28]=4)[OH:26])[CH:8]=3)[N:3]=2)[CH2:44][CH2:43][CH2:42]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 10422AzetidineHCID 118006215(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloroquinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Product 1

HCID 118006368{2-Azetidin-1-yl-4-chloro-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-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}(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (198 mg, 0.347 mmol, Example 151), azetidine (70 μL, 1.04 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 then 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 provide the title compound. MS (ESI): mass calcd. for C33H31ClN8O, 590.2. m/z found, 591.5 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 8.07-8.02 (m, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.64-7.56 (m, 2H), 7.38-7.31 (m, 1H), 7.08-6.99 (m, 4H), 6.98 (s, 1H), 6.88-6.77 (m, 2H), 5.89 (d, J=1.9 Hz, 1H), 4.29 (s, 2H), 4.12 (t, J=7.5 Hz, 4H), 3.93 (s, 3H), 2.47 (s, 3H), 2.34 (s, 3H), 2.31-2.18 (m, 2H).

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 materialthen dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-d1b4bae1aee6458692178e119ea17288
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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