Acetic Acid → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)(1-methylazetidin-3-yl)methanol

HRID 926617Notes

Reaction equation

HRID 926617 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[C:18]([O:23][CH3:24])[C:17]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)=[C:16]3[Cl:36])([C:7]2[N:11]([CH3:12])[N:10]=[N:9][CH:8]=2)[OH:6])[CH2:2]1.C=O.[C:39](O)(=O)C.C([BH3-])#N.[Na+]>CO>[Cl:36][C:16]1[C:15]2[C:20](=[CH:21][CH:22]=[C:13]([C:5]([C:7]3[N:11]([CH3:12])[N:10]=[N:9][CH:8]=3)([CH:3]3[CH2:4][N:1]([CH3:39])[CH2:2]3)[OH:6])[CH:14]=2)[N:19]=[C:18]([O:23][CH3:24])[C:17]=1[CH2:25][C:26]1[CH:27]=[CH:28][C:29]([C:32]([F:33])([F:35])[F:34])=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86715675azetidin-3-yl(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Product 1

HCID 118006124(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)(1-methylazetidin-3-yl)methanol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a flask containing azetidin-3-yl(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (252 mg, 0.49 mmol, Example 124) was added MeOH (5 mL), formaldehyde (0.5 mL, 6.72 mmol), acetic acid (0.15 mL, 2.62 mmol) and sodium cyanoborohydride (1 M solution in THF, 1 mL, 1 mmol) at room temperature. The reaction mixture was stirred at room temperature for 24 hours and then the contents were concentrated to dryness and the residue was dissolved in DCM. 1 N Aqueous NaOH was then added to adjust the pH of the solution to pH 10. The aqueous portion was extracted with DCM (3×25 mL) and CHCl3 (2×25 mL). The organics were combined, washed with brine, dried over MgSO4, filtered and concentrated to dryness. The residue was purified by FCC (2% 2 M NH3-MeOH increasing to 10% 2 M NH3-MeOH) to provide the title compound as an off white solid. 1H NMR (500 MHz, CDCl3) δ 8.34 (d, J=2.0 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.48-7.52 7.50 (m, 3H), 7.44-7.32 (m, 3H), 4.35 (s, 2H), 4.06 (s, 3H), 3.75 (s, 3H), 3.56-3.47 (m, 1H), 3.46-3.36 (m, 1H), 3.31-3.17 (m, 1H), 3.12-3.01 (m, 1H), 3.00-2.90 (m, 1H), 2.31 (s, 3H); MS (ESI): mass calcd: Chemical Formula: C26H25ClF3N5O2, Exact Mass: 531.2. m/z found 532.1 [M+H]+.

Workup

  1. concentrationthe contents were concentrated to dryness
  2. dissolutionthe residue was dissolved in DCM
  3. addition1 N Aqueous NaOH was then added
  4. extractionThe aqueous portion was extracted with DCM (3×25 mL) and CHCl3 (2×25 mL)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by FCC (2% 2 M NH3-MeOH increasing to 10% 2 M NH3-MeOH)

Sources & evidence

ORD record
ord-c50c98a1e0994ef4ba68b9082fa7d425
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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