1H-1,2,4-Triazole → HCID 19816046, compound

HRID 2247914Notes

Reaction equation

HRID 2247914 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.S(Cl)(Cl)=O.[CH:10]1([CH:13](O)[C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[NH:18][CH2:17]3)[CH2:12][CH2:11]1>O1CCOCC1>[CH:10]1([CH:13]([N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)[C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[NH:18][CH2:17]3)[CH2:11][CH2:12]1

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24386Thionyl ChlorideHCID 19816025HCID 19816025, compound

Product 1

HCID 19816046HCID 19816046, compoundYield 1.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred and cooled (15° C.) solution of 2.5 parts of 1H-1,2,4-triazole in 70 parts of 1,4-dioxane was added dropwise 1 part of thionyl chloride under nitrogen atmosphere. After stirring for 10 minutes at 20° C., a solution of 2 parts of 6-(cyclopropylhydroxymethyl)-3,4-dihydro-2(1H)-quinazolinone in 80 parts of 1,4-dioxane was added portionwise to the previous mixture at 20°-25° C. After stirring overnight at room temperature, the precipitated product was filtered off, washed with 1,4-dioxane and purified by column chromatography over silica gel using a mixture of dichloromethane, methanol and methanol, saturated with ammonia (90:5:5 by volume) as eluent. The eluent of the desired fraction was evaporated and the residue was further purified, first by column chromatography (HPLC) over silica gel using a mixture of dichloromethane and methanol (96:4 and 97.5:2.5 by volume) and then by column chromatography (RP 18) using a mixture of water and methanol (80:20 by volume) as eluents. The eluent of the desired fraction was evaporated and the residue was stirred in 2,2'-oxybispropane. The product was filtered off, washed with 2,2'-oxybispropane and dried in vacuo at 60° C., yielding 0.04 parts (1.7%) of 6-[cyclopropyl(1H-1,2-4-triazol-1-yl)methyl]-3,4-dihydro-2(1H)-quinazolinone; mp. 184.4° C. (comp. 25).

Workup

  1. stirringAfter stirring for 10 minutes at 20° C.
  2. stirringAfter stirring overnight at room temperature
  3. filtrationthe precipitated product was filtered off
  4. washwashed with 1,4-dioxane
  5. custompurified by column chromatography over silica gel using
  6. additiona mixture of dichloromethane, methanol and methanol
  7. customThe eluent of the desired fraction was evaporated
  8. additionfirst by column chromatography (HPLC) over silica gel using a mixture of dichloromethane and methanol (96:4 and 97.5:2.5 by volume)
  9. additiona mixture of water and methanol (80:20 by volume) as eluents
  10. customThe eluent of the desired fraction was evaporated
  11. stirringthe residue was stirred in 2,2'-oxybispropane
  12. filtrationThe product was filtered off
  13. washwashed with 2,2'-oxybispropane
  14. customdried in vacuo at 60° C.

Sources & evidence

ORD record
ord-2adeac65bf674f55a300351397e951a1
Source dataset
uspto-grants-1991_08
Patent number
US05037829

Reaction notes

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