N,N-Dimethyl-1,3-propanediamine → 3-[5-Chloro-3-[[3-(dimethylamino)propyl]amino]-2-oxo-1(2H)-pyrazinyl]-N-cyclopropyl-4-methyl-benzamide

HRID 337031Notes

Reaction equation

HRID 337031 reaction equation
Cl[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]([Cl:8])[N:7]=1.[CH3:21][N:22]([CH3:27])[CH2:23][CH2:24][CH2:25][NH2:26].[CH:28]1([NH2:31])[CH2:30][CH2:29]1.C([Mg]Cl)(C)C.[NH4+].[Cl-]>O1CCCC1>[Cl:8][C:6]1[N:7]=[C:2]([NH:26][CH2:25][CH2:24][CH2:23][N:22]([CH3:27])[CH3:21])[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:31][CH:28]2[CH2:30][CH2:29]2)=[O:14])[CH:5]=1

Participants

7

Reactant 5

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 25517Ammonium ChlorideHCID 69828CyclopropylamineHCID 866632353-(3,5-Dichloro-2-oxo-1(2H)-pyrazinyl)-4-methyl-benzoic acid, methyl esterHCID 178418918HCID 178418918, compound2×

Product 1

HCID 666864973-[5-Chloro-3-[[3-(dimethylamino)propyl]amino]-2-oxo-1(2H)-pyrazinyl]-N-cyclopropyl-4-methyl-benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-(3,5-dichloro-2-oxo-1(2H)-pyrazinyl)-4-methyl-benzoic acid, methyl ester (Example 107a, 200 mg) in tetrahydrofuran (3 mL) was added N,N-dimethyl-1,3-propanediamine (90 μL) and the mixture was stirred at room temperature for 12 h. Cyclopropylamine (220 μL) was added followed by the addition of iso-propylmagnesium chloride (2M in tetrahydrofuran, 1 mL) portionwise. The reaction mixture was stirred for 60 minutes and iso-propylmagnesium chloride (2M in tetrahydrofuran, 1 mL) was added. The mixture was stirred for an additional 30 minutes and sat. aqueous NH4Cl was added. The aqueous solution was extracted with ethyl acetate. The pooled organic was washed with brine and dried (MgSO4), filtered and the solvent removed. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) gave the title compound (149 mg).

Workup

  1. stirringThe reaction mixture was stirred for 60 minutes
  2. stirringThe mixture was stirred for an additional 30 minutes
  3. extractionThe aqueous solution was extracted with ethyl acetate
  4. washThe pooled organic was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed
  8. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-210e8725f58c477195e91f4dff5192cf
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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