Potassium Carbonate → N-Cyclopropyl-4-methyl-3-[3-[[1-methyl-1-[2-(4-piperidinylmethoxy)phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide

HRID 1697332Notes

Reaction equation

HRID 1697332 reaction equation
[CH:1]1([NH:4][C:5](=[O:31])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[OH:29])([CH3:22])[CH3:21])[C:14]3=[O:30])[CH:7]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:39][CH:40]1[CH2:45][CH2:44][N:43](C(OC(C)(C)C)=O)[CH2:42][CH2:41]1>C(#N)C>[CH:1]1([NH:4][C:5](=[O:31])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]([CH3:22])([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[O:29][CH2:39][CH:40]4[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]4)[CH3:21])[C:14]3=[O:30])[CH:7]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 66686301N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide

Product 1

HCID 66690547N-Cyclopropyl-4-methyl-3-[3-[[1-methyl-1-[2-(4-piperidinylmethoxy)phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamideYield 23.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N-Cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide (Example 134, 0.172 g), potassium carbonate (0.114 g) and tert-butyl 4-(bromomethyl)piperidine-1-carboxylate (0.114 g) were stirred together in acetonitrile (10 mL) at reflux overnight. The cooled reaction mixture was evaporated to dryness and the residue partitioned between ethyl acetate (20 mL) and water (20 mL). The separated aqueous layer was further extracted into ethyl acetate (2×20 mL), the combined organics were dried (MgSO4) and evaporated. The residue was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (1 ml), after stirring at room temperature for 1 h, the solvent was evaporated to leave the crude product. Purification by preparative HPLC (Gemini column—acetonitrile/0.2% ammonia mobile phase) afforded the title compound as a solid (50 mg).

Workup

  1. temperatureat reflux overnight
  2. customThe cooled reaction mixture
  3. customwas evaporated to dryness
  4. customthe residue partitioned between ethyl acetate (20 mL) and water (20 mL)
  5. extractionThe separated aqueous layer was further extracted into ethyl acetate (2×20 mL)
  6. dry with materialthe combined organics were dried (MgSO4)
  7. customevaporated
  8. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  9. additiontreated with trifluoroacetic acid (1 ml)
  10. customthe solvent was evaporated
  11. customto leave the crude product
  12. customPurification by preparative HPLC (Gemini column—acetonitrile/0.2% ammonia mobile phase)

Sources & evidence

ORD record
ord-f50dfb503b1e4d11a260885cc06ef80d
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

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