Acetic Acid → HCID 68651189, compound

HRID 646721Notes

Reaction equation

HRID 646721 reaction equation
[NH2:1][C:2]1[C:3]([C:16]([NH:18][CH3:19])=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=O)[CH:9]=2)=[CH:6][N:7]=1.[CH:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][C:21]=1[NH2:30].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C1COCC1>[NH2:1][C:2]1[C:3]([C:16]([NH:18][CH3:19])=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][NH:30][C:21]3[CH:22]=[CH:23][C:24]4[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:20]=3)[CH:9]=2)=[CH:6][N:7]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 70572-NaphthylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 58710602HCID 58710602, compound

Product 1

HCID 68651189HCID 68651189, compoundYield 26.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-amino-6-(3-formylphenyl)-N-methylpyrazine-2-carboxamide (0.075 g, 0.29 mmol), naphthalen-2-amine (0.21 g, 1.5 mmol), glacial AcOH (0.033 mL, 0.56 mmol) and NaBH(OAc)3 (0.093 g, 0.44 mmol) in THF (1.1 mL) was heated to 80° C. for 12 h. Upon cooling, saturated NaHCO3 (aq) was added (25 mL). The aqueous layer was extracted with EtOAc (2 x 25 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The crude mixture was purified via HPLC (reverse-phase, CH3CN/H2O with 0.1% TFA). Upon removal of CH3CN/H2O, the product was taken up in MeOH and treated with Bio-Rad AG 1-X8 resin (hydroxide form) until pH 8. The product was filtered and concentrated in vacuo, to provide 29.1 mg (26% yield) of 3-amino-N-methyl-6-{3-[(naphthalen-2-ylamino)methyl]phenyl}pyrazine-2-carboxamide: 1H NMR (400 MHz, 4-DMSO): 8.84 (s, 1H), 8.77 (d, 1H), 8.22 (s, 1H), 8.05 (dt, 1H), 7.62 (t, 2H), 7.51 (d, 1H), 7.41 (d, 2H), 7.27 (dt, 1H), 7.10 (dt, 2H), 6.77 (d, 1H), 6.57 (t, 1H), 4.46 (d, 2H), 2.85 (d, 3H); MS (EI) for C23H21N5O: 384 (MH+)

Workup

  1. temperatureUpon cooling
  2. extractionThe aqueous layer was extracted with EtOAc (2 x 25 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified via HPLC (reverse-phase, CH3CN/H2O with 0.1% TFA)
  7. customUpon removal of CH3CN/H2O
  8. additiontreated with Bio-Rad AG
  9. filtrationThe product was filtered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5c7856c779564c83b3d10d5161e06f6f
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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