Sodium Chloride → [4-Chloro-2-methoxy-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-6-yl]-(3-methyltriazol-4-yl)methanol

HRID 1507318Notes

Reaction equation

HRID 1507318 reaction equation
C([Li])CCC.[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22](Br)=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1.[CH3:32][N:33]1[C:37]([CH:38]=[O:39])=[CH:36][N:35]=[N:34]1.[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22]([CH:38]([C:37]3[N:33]([CH3:32])[N:34]=[N:35][CH:36]=3)[OH:39])=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 211875071-Methyl-1H-1,2,3-triazole-5-carbaldehyde2×HCID 867155963-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline2×HCID 178418339Butyllithium

Product 1

HCID 118005933[4-Chloro-2-methoxy-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-6-yl]-(3-methyltriazol-4-yl)methanol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of n-butyllithium in hexanes (1.6 M, 0.71 mL, 1.1 mmol) was added dropwise to a stirring solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (490 mg, 1.1 mmol, Intermediate 4: step d) in tetrahydrofuran (11 mL) at −78° C. After 2 minutes, a solution of 1-methyl-1H-1,2,3-triazole-5-carbaldehyde (140 mg, 1.1 mmol, Intermediate 18) in tetrahydrofuran (1 mL) was added dropwise. After 5 minutes, the flask was placed into an ice-water bath. After 1 hour, water (10 mL) and ethyl acetate (60 mL) were added. The biphasic mixture was stirred for 10 minutes. Half-saturated aqueous sodium chloride solution (50 mL) was added and the layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica gel (4 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 which was impure. The foam was suspended in methanol (20 mL) and the suspension was sonicated for 5 minutes. The solids were collected by filtration and rinsed with methanol (5 mL). The collected solids were dried to provide the title compound as a white solid. 1H NMR (600 MHz, DMSO-d6) δ ppm 8.42 (d, J=2.5 Hz, 1H), 8.21 (d, J=1.8 Hz, 1H), 7.86 (d, J=8.6 Hz, 1H), 7.75-7.71 (m, 2H), 7.72-7.67 (m, 2H), 7.37-7.32 (m, 3H), 6.55 (d, J=5.2 Hz, 1H), 6.53-6.49 (m, 1H), 6.22 (d, J=5.2 Hz, 1H), 4.30 (s, 2H), 4.04 (s, 3H), 3.97 (s, 3H); MS (ESI): mass calcd. for C24H21ClN6O2, 460.1; m/z found, 461.1 [M+H]+.

Workup

  1. waitAfter 5 minutes
  2. customthe flask was placed into an ice-water bath
  3. waitAfter 1 hour
  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 (4 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-c1a00e873014474bbfde0a0d8e90675c
Source dataset
uspto-grants-2015_12
Patent number
US09221804B2

Reaction notes

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