Formaldehyde → 8-(4-Methylpiperazin-1-yl)-5-(thiophen-2-yl)tetrazolo[1,5-a]pyrazine

HRID 1045736Notes

Reaction equation

HRID 1045736 reaction equation
Cl.[N:2]1([C:8]2[C:9]3[N:10]([N:19]=[N:20][N:21]=3)[C:11]([C:14]3[S:15][CH:16]=[CH:17][CH:18]=3)=[CH:12][N:13]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C=O.[CH2:24](Cl)Cl.C([O-])(O)=O.[Na+]>CO>[CH3:24][N:5]1[CH2:4][CH2:3][N:2]([C:8]2[C:9]3[N:10]([N:19]=[N:20][N:21]=3)[C:11]([C:14]3[S:15][CH:16]=[CH:17][CH:18]=3)=[CH:12][N:13]=2)[CH2:7][CH2:6]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 673934078-(piperazin-1-yl)-5-(thiophen-2-yl)tetrazolo[1,5-a]pyrazine HCl salt

Product 1

HCID 533637588-(4-Methylpiperazin-1-yl)-5-(thiophen-2-yl)tetrazolo[1,5-a]pyrazineYield 94%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 2 L round bottom flask was charged with 8-(piperazin-1-yl)-5-(thiophen-2-yl)tetrazolo[1,5-a]pyrazine HCl salt (139 g, 0.429 mol), HCHO (38% aqueous solution, 50 mL), NaBH3(CN) (90.7 g, 1.44 mol), CH2Cl2 (500 mL), and MeOH (200 mL). The resulting solution was stirred at room temperature for 0.5 h. Work-up: the reaction mixture was poured into saturated aqueous NaHCO3 and extracted with CH2Cl2 (500 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was further purified by flash column chromatography on silica gel with 1-10% MeOH in CH2Cl2, to afford 122 g (94%) of the product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ: 8.00 (m, 2H), 7.45 (dd, J=5.1, 1.2 Hz, 1H), 7.20 (dd, J=5.1, 3.6 Hz, 1H), 4.39 (br, 4H), 2.60 (t, J=5.1 Hz, 4H), 2.37 (s, 3H). MS m/z: 302 (M+H+).

Workup

  1. extractionextracted with CH2Cl2 (500 mL×3)
  2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was further purified by flash column chromatography on silica gel with 1-10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-6844445f0b22426896119d28f6d1d509
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

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