Hydrochloric Acid → 2-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide

HRID 929911Notes

Reaction equation

HRID 929911 reaction equation
O[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH2:14][C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:13]=2)[N:3]=1.Cl.O1CCOCC1.O=P(Cl)(Cl)[Cl:30]>C(#N)C>[Cl:30][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH2:14][C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:13]=2)[N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 312751,4-DioxaneHCID 178457882HCID 178457882, compound

Product 1

HCID 900240272-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 2-(4-(4-hydroxypyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide (6.0 g, 22 mmol) in acetonitrile (300 mL) was added 4M HCl in dioxane (12 mL, 48 mmol) then POCl3 (10 g). The mixture was heated to reflux for 0.5 h then concentrated in vacuo. The residue was slurried with water and adjusted to pH 9 with aqueous sodium hydrogen carbonate. The remaining solid was collected by filtration and purified by column chromatography (50% v/v DCM/ethyl acetate) to afford 2-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide II-1 (2.30 g, 36%) as a white solid. LC-MS (Method A), RT=8.28 min. (ES+) 295.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 0.5 h
  3. concentrationthen concentrated in vacuo
  4. filtrationThe remaining solid was collected by filtration
  5. custompurified by column chromatography (50% v/v DCM/ethyl acetate)

Sources & evidence

ORD record
ord-5ea791708718482c9a2b365a9070ff73
Source dataset
uspto-grants-2016_03
Patent number
US09296725B2

Reaction notes

Loading…