Acetic Acid → HCID 68650472, compound

HRID 646723Notes

Reaction equation

HRID 646723 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[CH:8]=O.[NH2:16][C:17]1[C:18]([C:31]([NH:33][CH3:34])=[O:32])=[N:19][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][NH2:30])[CH:24]=2)=[CH:21][N:22]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C1COCC1>[NH2:16][C:17]1[C:18]([C:31]([NH:33][CH3:34])=[O:32])=[N:19][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][NH:30][CH2:8][C:7]3[CH:6]=[CH:5][C:4]([C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)=[CH:3][C:2]=3[F:1])[CH:24]=2)=[CH:21][N:22]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 167685272-Fluoro-4-phenylbenzaldehydeHCID 58710591HCID 58710591, compound

Product 1

HCID 68650472HCID 68650472, compoundYield 20.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-fluorobiphenyl-4-carbaldehyde (0.030 g, 0.15 mmol), 3-amino-6-[3-(aminomethyl)phenyl]-N-methylpyrazine-2-carboxamide (0.038 g, 0.15 mmol), glacial AcOH (0.010 mmol, 0.15 mmol) and NaBH(OAc)3 (0.047 g, 0.22 mmol) in THF (0.6 mL) was stirred at r.t. for 12 h. Saturated NaHCO3 (aq) was added (25 mL) and the aqueous layer was extracted with EtOAc (2×25 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 13.4 mg (20% yield) of 3-amino-6-[3-({[(3-fluorobiphenyl4-yl)methyl]amino}methyl)phenyl]-N-methylpyrazine-2-carboxamide: 1H NMR (400 MHz, d6-DMSO): 8.84 (s, 1H), 8.79 (d, 1H), 8.09 (bs, 1H), 8.05 (m, 1H), 7.70 (m, 2H), 7.61 (t, 1H), 7.36-7.53 (m, 8H), 3.80 (d, 4H), 2.86 (d, 3H); MS (EI) for C26H24N5OF: 442 (MH+).

Workup

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

Sources & evidence

ORD record
ord-5ff00351419448cfb3141c839d58a48d
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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