Sodium hydride → HCID 178432773, compound

HRID 1914669Notes

Reaction equation

HRID 1914669 reaction equation
[Cl:1][C:2]1[C:3]([CH3:8])=[N:4][NH:5][C:6]=1[CH3:7].[H-].[Na+].[Cl:11][C:12]1[CH:13]=[C:14]([C:19]([NH:21][C@H:22]2[CH2:27][CH2:26][C@H:25]([CH2:28]OS(C)(=O)=O)[CH2:24][CH2:23]2)=[O:20])[C:15]([CH3:18])=[N:16][CH:17]=1>C(#N)C.O>[Cl:11][C:12]1[CH:17]=[N:16][C:15]([CH3:18])=[C:14]([CH:13]=1)[C:19]([NH:21][C@H:22]1[CH2:27][CH2:26][C@H:25]([CH2:28][N:4]2[C:3]([CH3:8])=[C:2]([Cl:1])[C:6]([CH3:7])=[N:5]2)[CH2:24][CH2:23]1)=[O:20]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 6736884-chloro-3,5-dimethyl-1H-pyrazoleHCID 178432776HCID 178432776, compound

Product 1

HCID 178432773HCID 178432773, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 4-chloro-3,5-dimethyl-1H-pyrazole (step 5a) (37 mg, 0.283 mmol) in dry acetonitrile (4.5 mL) at room temp is added sodium hydride (14 mg of a 60% dispersion in mineral oil, 0.353 mmol). The mixture is stirred at room temp for 10 minutes before trans-methanesulfonic acid 4-[(5-chloro-2-methyl-pyridine-3-carbonyl)-amino]-cyclohexylmethyl ester (step 4) (85 mg, 0.236 mmol) is added in one portion. The mixture is heated at 120° C. for 30 minutes using microwave radiation. After cooling to RT, the reaction mixture is diluted with water (10 mL) and extracted with EtOAc (3×10 mL). The EtOAc extracts are combined, washed with saturated brine (10 mL), dried (MgSO4), filtered and evaporated to give a colourless foam. Purification by chromatography on silica gel using a 12 g pre-packed column eluting with 0-100% EtOAc affords the title compound as a colourless solid. MS m/z 395.3/397.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.53 (1H, d), 8.39 (1H, d), 7.78 (1H, d), 3.83 (2H, d), 3.67 (1H, m), 2.47 (3H, s), 2.20 (3H, s), 2.09 (3H, s), 1.89 (2H, m), 1.73 (1H, m), 1.57 (2H, m), 1.16 (4H, m).

Workup

  1. additionis added in one portion
  2. temperatureAfter cooling to RT
  3. extractionextracted with EtOAc (3×10 mL)
  4. washwashed with saturated brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto give a colourless foam
  9. customPurification by chromatography on silica gel using a 12 g pre-packed column
  10. washeluting with 0-100% EtOAc

Sources & evidence

ORD record
ord-ffecbffc6fc14eec944c283fbc8eedcb
Source dataset
uspto-grants-2013_12
Patent number
US08614213B2

Reaction notes

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