Sodium Chloride → (4-Chloro-2-methoxy-3-(4-methylbenzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926586

Reaction equation

HRID 926586 reaction equation
C([Li])CCC.[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](I)[CH:15]=2)[N:10]=[C:9]([O:18][CH3:19])[C:8]=1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1.[CH3:28][C:29]1[C:34]([C:35]([C:37]2[N:41]([CH3:42])[N:40]=[N:39][CH:38]=2)=[O:36])=[CH:33][CH:32]=[C:31]([CH3:43])[N:30]=1.[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:35]([C:34]3[C:29]([CH3:28])=[N:30][C:31]([CH3:43])=[CH:32][CH:33]=3)([C:37]3[N:41]([CH3:42])[N:40]=[N:39][CH:38]=3)[OH:36])[CH:15]=2)[N:10]=[C:9]([O:18][CH3:19])[C:8]=1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 86715642(2,6-Dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone2×HCID 1180062494-Chloro-6-iodo-2-methoxy-3-(4-methylbenzyl)quinoline2×HCID 178418339Butyllithium

Product 1

HCID 118006555(4-Chloro-2-methoxy-3-(4-methylbenzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of n-butyllithium in hexanes (2.5 M, 0.47 mL, 1.2 mmol) was added dropwise to a stirring solution of 4-chloro-6-iodo-2-methoxy-3-(4-methylbenzyl)quinoline (500 mg, 1.2 mmol, Intermediate 22: step c) in tetrahydrofuran (9 mL) at −78° C. After 2 minutes, a solution of (2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone (255 mg, 1.2 mmol, Intermediate 19: step b) in tetrahydrofuran (2 mL) was added dropwise. After 5 minutes, the flask was placed into an ice-water bath. After 15 minutes, water (5 mL) and ethyl acetate (50 mL) were added and the biphasic mixture was poured into saturated aqueous sodium chloride solution (15 mL). The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica gel (6 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 100% hexanes initially, grading to 100% ethyl acetate provided the title compound as a white foam. MS (ESI): mass calcd. for C29H28ClN5O2, 513.2. m/z found, 514.1 [M+H]+.

Workup

  1. waitAfter 5 minutes
  2. customthe flask was placed into an ice-water bath
  3. waitAfter 15 minutes
  4. customThe layers were separated
  5. dry with materialThe organic layer was dried with sodium sulfate
  6. filtrationthe dried solution was filtered
  7. additionSilica gel (6 g) was added to the filtrate
  8. concentrationthe mixture was concentrated by rotary evaporation
  9. customto afford a free-flowing powder
  10. customThe powder was loaded onto a silica gel column for flash column chromatography purification
  11. washElution with 100% hexanes initially

Sources & evidence

ORD record
ord-354b2189a2ba46c38d1de97039a17ee7
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Linked notes

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