Cyclopropylamine → N-Cyclopropyl-4-methyl-3-[2-oxo-3-[[(2S)-2-phenylpropyl]amino]-1(2H)-pyrazinyl]benzamide

HRID 1697281Notes

Reaction equation

HRID 1697281 reaction equation
Br[C:2]1[C:3](=[O:20])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:12]([O:14]C)=O)[CH:5]=[C:6](Br)[N:7]=1.C([N:24](CC)[CH:25]([CH3:27])[CH3:26])(C)C.[C:30]1([C@H:36]([CH3:39])[CH2:37][NH2:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C1(N)CC1.C1([Mg]Br)CCCC1>O1CCCC1>[CH:25]1([NH:24][C:12](=[O:14])[C:11]2[CH:16]=[CH:17][C:18]([CH3:19])=[C:9]([N:4]3[CH:5]=[CH:6][N:7]=[C:2]([NH:38][CH2:37][C@H:36]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH3:39])[C:3]3=[O:20])[CH:10]=2)[CH2:26][CH2:27]1

Participants

7

Reactant 5

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 1547950(2S)-2-Phenylpropan-1-amineHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 178419650HCID 178419650, compound

Product 1

HCID 66685984N-Cyclopropyl-4-methyl-3-[2-oxo-3-[[(2S)-2-phenylpropyl]amino]-1(2H)-pyrazinyl]benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 0.1 g), N,N-diisopropylethylamine (0.1 mL), (S)-2-phenyl-1-propylamine (0.05 mL) and tetrahydrofuran (1 mL) was stirred at room temperature overnight. Cyclopropylamine (0.2 mL) was added followed by the addition of cyclopentylmagnesium bromide (2M in diethyl ether, 0.8 mL). The mixture was stirred for 10 min., quenched with sat. NH4Cl and extracted into ethyl acetate. The organic phase concentrated in vacuo. The residue was treated with ethanol (5 mL), wet 10% palladium on carbon (45 mg) was added followed by N,N-diisopropylethylamine (0.1 mL) and ammonium formate (0.4 g). The mixture was stirred under nitrogen atmosphere at 70° C. for 30 min. The mixture was filtered through a pad of Celite and the filtrate concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound as a solid (64 mg).

Workup

  1. stirringThe mixture was stirred for 10 min.
  2. customquenched with sat. NH4Cl
  3. extractionextracted into ethyl acetate
  4. concentrationThe organic phase concentrated in vacuo
  5. additionThe residue was treated with ethanol (5 mL), wet 10% palladium on carbon (45 mg)
  6. additionwas added
  7. stirringThe mixture was stirred under nitrogen atmosphere at 70° C. for 30 min
  8. filtrationThe mixture was filtered through a pad of Celite
  9. concentrationthe filtrate concentrated in vacuo
  10. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-22ab0d5d3ed24d62817430821a655b5f
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

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