Benzylamine → 3-[5-Chloro-2-oxo-3-[(phenylmethyl)amino]-1(2H)-pyrazinyl]-N-cyclopropyl-4-methyl-benzamide

HRID 337032Notes

Reaction equation

HRID 337032 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.[CH2:21]([NH2:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[CH:29]1([NH2:32])[CH2:31][CH2:30]1.C([Mg][Cl:37])(C)C>O1CCCC1.[Pd].C(O)=O.C(O)C.C(N(CC)CC)C>[Cl:37][C:6]1[N:7]=[C:2]([NH:28][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:3](=[O:20])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:12]([NH:32][CH:29]2[CH2:31][CH2:30]2)=[O:14])[CH:5]=1

Participants

10

Reactant 4

HCID 7504BenzylamineHCID 69828CyclopropylamineHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 178418918HCID 178418918, compound

Product 1

HCID 666859923-[5-Chloro-2-oxo-3-[(phenylmethyl)amino]-1(2H)-pyrazinyl]-N-cyclopropyl-4-methyl-benzamide

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 0.2 g) in tetrahydrofuran (3 mL) within a microwave vial was added triethylamine (76 μL) and benzylamine (64 mg). The reaction was stirred overnight before the addition of cyclopropylamine (0.22 mL) and iso-propylmagnesium chloride (2M in tetrahydrofuran, 1.5 mL) dropwise. After stirring for 30 minutes, ethanol (2 mL), formic acid (0.4 mL) and 10% palladium on carbon (30 mg) were added. The reaction mixture was heated within a microwave for 60 minutes at 110° C. before being cooled to room temperature, filtered and washed with ethanol. The filtrate was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound (80 mg).

Workup

  1. temperaturebefore being cooled to room temperature
  2. filtrationfiltered
  3. washwashed with ethanol
  4. concentrationThe filtrate was concentrated in vacuo
  5. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-91a66987cacf44f8ab4bc4162e2a7805
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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