Formic Acid → 8-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-3-(4-methoxy-phenyl)-7-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

HRID 2102314Notes

Reaction equation

HRID 2102314 reaction equation
[CH:1](O)=O.C=O.C([BH3-])#N.[Na+].[Cl:10][C:11]1[CH:12]=[C:13]([C:17]2[N:21]=[C:20]([CH:22]3[NH:27][CH2:26][CH2:25][N:24]4[C:28]([C:31]5[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=5)=[N:29][N:30]=[C:23]34)[O:19][N:18]=2)[CH:14]=[CH:15][CH:16]=1>CO.O>[Cl:10][C:11]1[CH:12]=[C:13]([C:17]2[N:21]=[C:20]([CH:22]3[N:27]([CH3:1])[CH2:26][CH2:25][N:24]4[C:28]([C:31]5[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=5)=[N:29][N:30]=[C:23]34)[O:19][N:18]=2)[CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 284Formic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 11338795HCID 11338795, compound

Product 1

HCID 114075718-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-3-(4-methoxy-phenyl)-7-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazineYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Formic acid (0.1 mL), formaldehyde (37 wt. % solution in water, 0.1 mL) and sodium cyanoborohydride (1.0 M in THF, 0.1 mL) were added to a solution of 8-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-3-(4-methoxy-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (30 mg, 0.071 mmol) in methanol (0.8 mL) at room temperature. After stirring for 30 minutes, the reaction mixture was diluted with water and then extracted with chloroform (4 times), dried over anhydrous sodium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel; using 50% ethyl acetate in hexanes, ethyl acetate and 4% 2M ammonia in methanol in dichloromethane afforded the titled compound (23.8 mg, 77%). 1H NMR (CDCl3) δ (ppm): 8.04 (m, 1H), 7.93 (m, 1H), 7.68 (m, 2H), 7.42 (m, 2H), 7.03 (m, 2H), 4.37 (m,1H), 4.07 (m, 2H), 3.89 (m, 3H), 3.82 (m, 2H), 3.11 (m, 1H), 2.88 (m, 1H), 2.56 s, 3H).

Workup

  1. extractionextracted with chloroform (4 times)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-9c0e1c31c16e409192ac70b31366bc5b
Source dataset
uspto-grants-2009_08
Patent number
US07576077B2

Reaction notes

Loading…