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

HRID 337021Notes

Reaction equation

HRID 337021 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:21]1([C@H:27]([CH3:30])[CH2:28][NH2:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH:31]1([NH2:34])[CH2:33][CH2:32]1.C1([Mg]Br)CCCC1>O1CCCC1>[CH:31]1([NH:34][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:29][CH2:28][C@H:27]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH3:30])[C:3]3=[O:20])[CH:10]=2)[CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 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-diisopropylethylamnie (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-diisopropylethylamnie (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-1aa98f456da84db0966df5bac3842004
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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