2-Methylpyridine → HCID 58920622, compound

HRID 1365508Notes

Reaction equation

HRID 1365508 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[Cl:13][C:14]1[CH:15]=[CH:16][C:17](/[C:20](/[C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([F:38])[CH:29]=2)=[N:21]\[S@@:22]([C:24]([CH3:27])([CH3:26])[CH3:25])=[O:23])=[N:18][CH:19]=1>C1COCC1>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C@@:20]([NH:21][S@:22]([C:24]([CH3:27])([CH3:26])[CH3:25])=[O:23])([C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([F:38])[CH:29]=2)[CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)=[N:18][CH:19]=1

Participants

5

Reactant 3

HCID 79752-MethylpyridineHCID 87171037HCID 87171037, compoundHCID 178418339Butyllithium

Product 1

HCID 58920622HCID 58920622, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

2-Methyl pyridine (48 μL, 0.49 mmol) in THF (90 μL) was cooled at −78° C. for 10 min, followed by the addition of n-BuLi (246 μL, 0.49 mmol, 2M solution in cyclohexane). The reaction turned into maroon and was stirred at −78° C. for 40 min. (R,Z)-N-((5-chloropyridin-2-yl)(3-fluoro-5-(trifluoromethyl)phenyl)methylene)-2-methylpropane-2-sulfinamide (100 mg, 0.25 mmol) in THF (1 mL) was added and the dark green colored reaction mixture was stirred at −78° C. for another 2 h. Quenched with H2O (10 mL), the reaction mixture was extracted by EtOAc (2×15 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified by preparative HPLC YMC ODS S5 28×100 mm Ballistic column 40-100% MeOH (90% in water, 0.1% TFA) gradient over 12 min with flow rate 40 mL/min and UV detection at 220 nm. (S)-N-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(pyridin-2-yl)ethyl)-2-methylpropane-2-sulfinamide at a retention time of 9.66 min and was isolated as a clear oil (48 mg, yield 38%) LCMS: 1.76 min [M+1] 500.2 (2 min gradient, MeOH/H2O 0.1% TFA); HPLC: 3.72 min (4 min gradient, MeOH/H2O 0.2% PPA); Purity 100%; NMR: 400 MHz 1H (CDCl3) 8.45 ppm, 1 H, d, J=2.64 Hz; 8.28 ppm, 1 H, d, J=4.39 Hz; 7.93 ppm, 1 H, s; 7.68 ppm, 1 H, d, J=8.79 Hz; 7.48 ppm, 1 H, dd, J=8.57, 2.42 Hz; 7.35 ppm, 1 H, t, J=6.81 Hz; 7.31 ppm, 1 H, s; 7.10 ppm, 1 H, d, J=7.91 Hz; 6.97 ppm, 2 H, m; 6.79 ppm, 1 H, d, J=7.47 Hz; 4.10 ppm, 1 H, d, J=14.06 Hz; 3.86 ppm, 1 H, d, J=14.50 Hz; 1.25 ppm, 9 H, s.

Workup

  1. additionwas added
  2. customQuenched with H2O (10 mL)
  3. extractionthe reaction mixture was extracted by EtOAc (2×15 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC YMC ODS S5 28×100 mm Ballistic column 40-100% MeOH (90% in water, 0.1% TFA) gradient over 12 min with flow rate 40 mL/min and UV detection at 220 nm

Sources & evidence

ORD record
ord-1787e228c9234d84aeda450388761f13
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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