(2,6-Dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone → (3-(4-(1H-1,2,4-Triazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926588Notes

Reaction equation

HRID 926588 reaction equation
[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([O:23][CH3:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17](I)=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1.[CH3:27][C:28]1[C:33]([C:34]([C:36]2[N:40]([CH3:41])[N:39]=[N:38][CH:37]=2)=[O:35])=[CH:32][CH:31]=[C:30]([CH3:42])[N:29]=1>O1CCCC1>[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([O:23][CH3:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:34]([C:33]3[C:28]([CH3:27])=[N:29][C:30]([CH3:42])=[CH:31][CH:32]=3)([C:36]3[N:40]([CH3:41])[N:39]=[N:38][CH:37]=3)[OH:35])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

4

Reactant 2

HCID 86715642(2,6-Dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone2×HCID 1180061563-(4-(1H-1,2,4-Triazol-1-yl)benzyl)-4-chloro-6-iodo-2-methoxyquinoline2×

Product 1

HCID 118006133(3-(4-(1H-1,2,4-Triazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
23 °C

Procedure

A solution of isopropylmagnesium chloride-lithium chloride complex in tetrahydrofuran (1.3 M, 0.79 mL, 1.0 mmol) was added dropwise to an ice-water cooled, stirring solution of 3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-4-chloro-6-iodo-2-methoxyquinoline (325 mg, 0.682 mmol, Intermediate 20: step c) in dry tetrahydrofuran (5 mL). After 15 minutes, a solution of (2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone (177 mg, 0.818 mmol, Intermediate 19: step b) in tetrahydrofuran (1.5 mL) was added dropwise. After 10 minutes, the flask was removed from the cooling bath and allowed to warm to 23° C. After 4 hours, water (5 mL) was added. The mixture was partitioned between saturated aqueous sodium chloride solution (25 mL) and ethyl acetate (50 mL). The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica gel (5 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica gel column for flash column chromatography purification. Elution with dichloromethane initially, grading to 10% methanol-dichloromethane provided the title compound as a white solid. MS (ESI): mass calcd. for C30H27ClN8O2, 566.2. m/z found, 567.0 [M+H]+.

Workup

  1. temperaturecooled
  2. waitAfter 10 minutes
  3. customthe flask was removed from the cooling bath
  4. waitAfter 4 hours
  5. additionwater (5 mL) was added
  6. customThe mixture was partitioned between saturated aqueous sodium chloride solution (25 mL) and ethyl acetate (50 mL)
  7. customThe layers were separated
  8. dry with materialThe organic layer was dried with sodium sulfate
  9. filtrationthe dried solution was filtered
  10. additionSilica gel (5 g) was added to the filtrate
  11. concentrationthe mixture was concentrated by rotary evaporation
  12. customto afford a free-flowing powder
  13. customThe powder was loaded onto a silica gel column for flash column chromatography purification
  14. washElution with dichloromethane initially

Sources & evidence

ORD record
ord-ac5dfb936553409b894f68b4806a029b
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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