1-Methyl-1H-1,2,3-triazole → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(3,5-dimethylisoxazol-4-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926618Notes

Reaction equation

HRID 926618 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[N:3]1.[Li]CCCC.[Cl:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]([C:25]3[C:26]([CH3:31])=[N:27][O:28][C:29]=3[CH3:30])=[O:24])[CH:21]=2)[N:16]=[C:15]([O:32][CH3:33])[C:14]=1[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=1>C1COCC1>[Cl:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]([C:25]3[C:26]([CH3:31])=[N:27][O:28][C:29]=3[CH3:30])([C:6]3[N:2]([CH3:1])[N:3]=[N:4][CH:5]=3)[OH:24])[CH:21]=2)[N:16]=[C:15]([O:32][CH3:33])[C:14]=1[CH2:34][C:35]1[CH:36]=[CH:37][C:38]([C:41]([F:43])([F:42])[F:44])=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 1401191-Methyl-1H-1,2,3-triazoleHCID 118006246(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(3,5-dimethylisoxazol-4-yl)methanone2×HCID 178418339Butyllithium

Product 1

HCID 118006262(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(3,5-dimethylisoxazol-4-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-43 °C

Procedure

To a flask containing 1-methyl-1H-1,2,3-triazole (200 mg, 2.41 mmol) was added THF (17 mL) and the solution was cooled to −43° C. using a CH3CN—CO2 bath. n-BuLi, (2.5 M in hexanes, 0.88 mL, 2.19 mmol) was then added dropwise to provide a white suspension. The suspension was stirred at −40° C. for 20 minutes, then a homogeneous solution of (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(3,5-dimethylisoxazol-4-yl)methanone (500 mg, 1.05 mmol, Intermediate 63: step b) in 2 mL THF was introduced. A dark brownish solution immediately resulted. The reaction mixture was allowed to warm gradually to 0° C. over 25 minutes, then was quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc (3×35 mL) and the combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. The residue was purified by FCC (20% EtOAc-hexanes increasing to 50% EtOAc) to provide the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.08 (d, J=2.1 Hz, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.61-7.46 (m, 3H), 7.39 (d, J=8.1 Hz, 2H), 6.94 (s, 1H), 4.81 (s, 1H), 4.32 (s, 2H), 4.09 (s, 3H), 3.98 (s, 3H), 1.95 (s, 3H), 1.82 (s, 3H); MS (ESI): mass calc. for Chemical Formula: C27H23ClF3N5O3; Exact Mass: 557.1. m/z found, 557.9 (M+H).

Workup

  1. customto provide a white suspension
  2. customA dark brownish solution immediately resulted
  3. temperatureto warm gradually to 0° C. over 25 minutes
  4. customwas quenched with aqueous NH4Cl solution
  5. extractionThe aqueous portion was extracted with EtOAc (3×35 mL)
  6. washthe combined organics were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe residue was purified by FCC (20% EtOAc-hexanes increasing to 50% EtOAc)

Sources & evidence

ORD record
ord-e7a3709d140c4cb38dd963b1711c2135
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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