Sodium ethoxide → (R)-tert-Butyl 1-(3-(3-chloro-4-cyano-2-methylphenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamate

HRID 872566Notes

Reaction equation

HRID 872566 reaction equation
[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([C:11]2[CH:15]=[CH:14][NH:13][N:12]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[O-]CC.[Na+].CS(O[CH2:25][C@H:26]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH3:27])(=O)=O>C(#N)C>[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([C:11]2[CH:15]=[CH:14][N:13]([CH2:27][C@H:26]([NH:28][C:29](=[O:30])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH3:25])[N:12]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 14427185(R)-2-((tert-butoxycarbonyl)amino)propyl methanesulfonateHCID 178422100HCID 178422100, compound

Product 1

HCID 67171349(R)-tert-Butyl 1-(3-(3-chloro-4-cyano-2-methylphenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamateYield 50.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

2-chloro-3-methyl-4-(1H-pyrazol-3-yl)benzonitrile (0.5 g, 2.297 mmol) was dissolved in dry acetonitrile (5 ml) under nitrogen and cooled to 0° C. Sodium ethoxide (0.313 g, 4.59 mmol) was added and the reaction mixture was stirred for 25 min and allowed to warm up to RT. (R)-2-(tert-butoxycarbonylamino)propyl methanesulfonate (0.582 g, 2.297 mmol) was dissolved in 5 ml of dry acetonitrile and added dropwise to the reaction mixture. The reaction mixture was refluxed for 15 h and then the solvents were evaporated. The residue was taken into EtOAc, washed several times with saturated aqueous NaHCO3 and water, dried with Na2SO4 and evaporated to dryness. CombiFlash purification afforded 0.437 g of the title compound using heptane/EtOAc-system as an eluent. 1H-NMR (400 MHz; d6-DMSO): δ 1.02 (d, 3H), 1.31 (s, 9H), 2.57 (s, 3H), 3.91 (m, 1H), 4.13 (m, 2H), 6.62 (m, 1H), 6.87 (d, 1H), 7.66 (d, 1H), 7.78 (d, 1H), 7.83 (d, 1H).

Workup

  1. temperatureto warm up to RT
  2. additionadded dropwise to the reaction mixture
  3. temperatureThe reaction mixture was refluxed for 15 h
  4. customthe solvents were evaporated
  5. washwashed several times with saturated aqueous NaHCO3 and water
  6. dry with materialdried with Na2SO4
  7. customevaporated to dryness
  8. customCombiFlash purification

Sources & evidence

ORD record
ord-cd301dde5c9344b0830433a698f60963
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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