Acetonitrile → p38alpha Inhibitor 2

HRID 1697314Notes

Reaction equation

HRID 1697314 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9]Cl.[CH:11]1([NH:14][C:15](=[O:41])[C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([N:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[OH:39])([CH3:32])[CH3:31])[C:24]3=[O:40])[CH:17]=2)[CH2:13][CH2:12]1.[C:42](#[N:44])C>>[CH:11]1([NH:14][C:15](=[O:41])[C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([N:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([CH3:32])([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[O:39][CH2:8][CH2:9][NH:44][CH3:42])[CH3:31])[C:24]3=[O:40])[CH:17]=2)[CH2:13][CH2:12]1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 78491-Bromo-2-ChloroethaneHCID 11430Potassium CarbonateHCID 66686301N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide

Product 1

HCID 25145735p38alpha Inhibitor 2

Conditions

Temperature
83 °C

Procedure

Potassium carbonate (330 mg) and 1-bromo-2-chloroethane (0.2 mL) were added to a stirred solution of N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide (Example 134, 0.1 g) in acetonitrile (5 mL). The reaction mixture was stirred under nitrogen at 83° C. for 16 h then concentrated in vacuo. The residue was treated with water and extracted into dichloromethane. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue (120 mg) was treated with 33% methylamine in ethanol (3 mL) and heated within a microwave at 100° C. for 60 minutes. The mixture was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound as a solid (65 mg).

Workup

  1. concentrationthen concentrated in vacuo
  2. additionThe residue was treated with water
  3. extractionextracted into dichloromethane
  4. washThe organic phase was washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionThe residue (120 mg) was treated with 33% methylamine in ethanol (3 mL)
  9. temperatureheated within a microwave at 100° C. for 60 minutes
  10. concentrationThe mixture was concentrated in vacuo
  11. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-3ae75d1a62854bc2934372c5c4aacb47
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

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