Thiophene-2-carbohydrazide → HCID 178508342, compound

HRID 646758Notes

Reaction equation

HRID 646758 reaction equation
[NH2:1][C:2]1[C:3]([C:16]#[N:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][OH:15])[CH:9]=2)=[CH:6][N:7]=1.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23]([NH:25][NH2:26])=O.C[O-].[Na+]>CO>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH2:14][OH:15])[CH:11]=[CH:12][CH:13]=2)=[N:4][C:3]=1[C:16]1[NH:26][N:25]=[C:23]([C:19]2[S:18][CH:22]=[CH:21][CH:20]=2)[N:17]=1

Participants

5

Reactant 3

HCID 73098Thiophene-2-carbohydrazideHCID 10942334Sodium MethoxideHCID 587105723-Amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile

Product 1

HCID 178508342HCID 178508342, compoundYield 6.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile (149 mg, 0.74 mmol) was added thiophene-2-carboxylic acid hydrazide (94 mg, 0.66 mmol), sodium methoxide (53 mg, 0.996 mmol) in MeOH (5 mL). After reflux for 4 days, the reaction mixture was extracted with ethyl acetate (10 mL×3) and dried over MgSO4. Filteraction and concentration in vacuo gave a crude product, which was purified by preparative HPLC (0.1% TFA in water/0.1% TFA in CH3CN). The product fractions were neutralized by aqueous saturated sodium bicarbonate solution and partitioned with ethyl acetate. The aqueous phase was extracted once with additional ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride then dried over anhydrous magnesium sulfate. Filtration and concentration in vacuo gave the (3-{5-amino-6-[3-(2-thienyl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl } phenyl)methanol (14 mg, yield): 1H NMR (400 MHz, CD3OD): δ 8.65 (s, 1H), 8.14 (s, 1H), 8.02 (d, 1H), 7.77 (m, 1H), 7.53 (m, 1H), 7.47 (m, 1H), 7.38 (m, 1H), 7.17 (m, 1H), 4.72 (s, 2H); MS (EI) for C17H14N6O: 351.10 (MH+).

Workup

  1. temperatureAfter reflux for 4 days
  2. extractionthe reaction mixture was extracted with ethyl acetate (10 mL×3)
  3. dry with materialdried over MgSO4
  4. concentrationFilteraction and concentration in vacuo
  5. customgave a crude product, which
  6. customwas purified by preparative HPLC (0.1% TFA in water/0.1% TFA in CH3CN)
  7. custompartitioned with ethyl acetate
  8. extractionThe aqueous phase was extracted once with additional ethyl acetate
  9. washThe combined organic layers were washed with saturated aqueous sodium chloride
  10. dry with materialthen dried over anhydrous magnesium sulfate
  11. filtrationFiltration and concentration in vacuo

Sources & evidence

ORD record
ord-2a00e6cfa46743768aef5eed1863e213
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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