Hydrochloric Acid → HCID 86660769, compound

HRID 1046834Notes

Reaction equation

HRID 1046834 reaction equation
N[C:2]1[N:31]=[C:5]2[N:6]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:7]([CH3:20])=[C:8]([C:18]#[N:19])[C@@H:9]([C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=3)[N:4]2[N:3]=1.N([O-])=O.[Na+].[S:36](=[O:38])=[O:37].[ClH:39]>C(O)(=O)C.O.[Cu]Cl>[C:18]([C:8]1[C@@H:9]([C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[N:4]2[N:3]=[C:2]([S:36]([Cl:39])(=[O:38])=[O:37])[N:31]=[C:5]2[N:6]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[C:7]=1[CH3:20])#[N:19]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1119Sulfur DioxideHCID 23668193Sodium NitriteHCID 66627900HCID 66627900, compound

Product 1

HCID 86660769HCID 86660769, compound

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 176Acetic AcidSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
1 °C

Procedure

(7R)-2-Amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (400 mg, 1.0 mmol; Example 7, free base) was dissolved in a mixture of acetic acid, conc. hydrochloric acid and water (2:1:1, 10 ml) at RT. At −10° C., a solution of sodium nitrite (72 mg, 1.0 mmol, 1.1 eq.) in water (1.1 ml) was slowly added dropwise to the reaction mixture. The mixture was allowed to warm to 0-2° C. and then cooled once more to −10° C. This solution was added to a solution of glacial acetic acid (11 ml) whose temperature had been adjusted to −10° C. beforehand and which had been saturated with sulfur dioxide gas and to which copper(I) chloride (18.8 mg, 0.019 mmol, 0.2 eq.) had been added. For a short while, there was a vigorous reaction. The mixture was stirred at −10° C. for 1 h, then warmed to 15° C. and stirred for another 1 h. The reaction solution was then once more cooled to 0° C. The product was precipitated by dropwise addition of this reaction solution to stirred ice-water (60 ml). The beige precipitate was filtered off, taken up in ethyl acetate, washed with saturated sodium chloride solution and then dried over sodium sulfate. After filtration, the mixture was concentrated under reduced pressure and the residue was dried under high vacuum. The product was obtained as a solid (415 mg, 63% pure, 55% of theory).

Workup

  1. temperaturecooled once more to −10° C
  2. customhad been adjusted to −10° C.
  3. additionhad been added
  4. customa vigorous reaction
  5. temperaturewarmed to 15° C.
  6. stirringstirred for another 1 h
  7. temperatureThe reaction solution was then once more cooled to 0° C
  8. customThe product was precipitated by dropwise addition of this reaction solution
  9. stirringto stirred ice-water (60 ml)
  10. filtrationThe beige precipitate was filtered off
  11. washwashed with saturated sodium chloride solution
  12. dry with materialdried over sodium sulfate
  13. filtrationAfter filtration
  14. concentrationthe mixture was concentrated under reduced pressure
  15. customthe residue was dried under high vacuum
  16. customThe product was obtained as a solid (415 mg, 63% pure, 55% of theory)

Sources & evidence

ORD record
ord-05024967dba74888bd6870c34b95db05
Source dataset
uspto-grants-2013_10
Patent number
US08569314B2

Reaction notes

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