2-Chloropyridine → HCID 71488733, compound

HRID 872071Notes

Reaction equation

HRID 872071 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C@H:11]2[CH2:13][C@@H:12]2[CH2:14][O:15][C:16]2[C:21]([CH2:22][OH:23])=[CH:20][N:19]=[C:18]([CH3:24])[N:17]=2)=[N:9][CH:10]=1.Cl[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1>C1COCC1>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C@H:11]2[CH2:13][C@@H:12]2[CH2:14][O:15][C:16]2[C:21]([CH2:22][O:23][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[CH:20][N:19]=[C:18]([CH3:24])[N:17]=2)=[N:9][CH:10]=1

Participants

5

Reactant 3

HCID 79772-ChloropyridineHCID 24758Sodium hydrideHCID 117689132HCID 117689132, compound

Product 1

HCID 71488733HCID 71488733, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

NaH (4 mg, 0.10 mmol, 60% disp.) was added in one portion to a stirring solution of (4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methylpyrimidin-5-yl)methanol (15 mg, 0.05 mmol) and 2-chloropyridine (11.3 mg, 0.1 mmol) in THF (0.33 mL) in a small pressure vessel. The vessel was sealed and then heated to 100° C. for 2 h. The reaction mixture was cooled to room temperature and then quenched by addition of 2 drops of saturated aqueous NaHCO3. The reaction mixture was diluted with EtOAc (5 mL) and washed sequentially with saturated aqueous NaHCO3 (5 mL) and brine (5 mL). The organics were dried over MgSO4, filtered, and concentrated in vacuo. The resulting residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-95% acetonitrile in water with 0.1% TFA modifier) to afford the title compound as a white solid. 1H NMR (500 MHz, DMSO): δ 8.44 (s, 1 H), 8.13-8.16 (m, 2H), 7.57 (td, J=7.2, 2.0 Hz, 1 H), 7.07 (dd, J=8.5, 2.9 Hz, 1 H), 7.02 (d, J=8.6 Hz, 1 H), 6.88 (dd, J=6.4, 5.4 Hz, 1 H), 6.77 (d, J=8.3 Hz, 1 H), 5.34 (s, 2H), 4.10-4.49 (m, 2 H), 3.82 (s, 3 H), 2.52 (s, 3 H), 2.06 (dt, J=8.3, 4.9 Hz, 1 H), 1.80-1.85 (m, 1 H), 1.26 (dt, J=8.6, 5.1 Hz, 1 H), 1.03 (dt, J=8.6, 4.9 Hz, 1 H); LRMS m/z (M+H) 379.4 found, 379.2 required.

Workup

  1. customThe vessel was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched by addition of 2 drops of saturated aqueous NaHCO3
  4. additionThe reaction mixture was diluted with EtOAc (5 mL)
  5. washwashed sequentially with saturated aqueous NaHCO3 (5 mL) and brine (5 mL)
  6. dry with materialThe organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-95% acetonitrile in water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-2aab3a17b86a411c9f102fcf2375d581
Source dataset
uspto-grants-2015_03
Patent number
US08975261B2

Reaction notes

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