Sulfur Dioxide → HCID 86664123, compound

HRID 2361911Notes

Reaction equation

HRID 2361911 reaction equation
N[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][C:3]=1[C@@H:10]1[C:15]([C:16]#[N:17])=[C:14]([CH3:18])[N:13]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[C:12](=[O:29])[NH:11]1.[ClH:30].O.N([O-])=O.[Na+].[S:36](=[O:38])=[O:37]>O.C(O)(=O)C.[Cu]Cl>[C:8]([C:6]1[CH:5]=[CH:4][C:3]([C@@H:10]2[C:15]([C:16]#[N:17])=[C:14]([CH3:18])[N:13]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:28])[F:26])[CH:20]=3)[C:12](=[O:29])[NH:11]2)=[C:2]([S:36]([Cl:30])(=[O:38])=[O:37])[CH:7]=1)#[N:9]

Participants

8

Reactant 4

HCID 1119Sulfur DioxideHCID 21885828Hydrate;hydrochlorideHCID 23668193Sodium NitriteHCID 66734667HCID 66734667, compound

Product 1

HCID 86664123HCID 86664123, compound

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 176Acetic AcidSolvent2×HCID 962WaterSolvent

Conditions

Temperature
-10 °C

Procedure

Under argon, (4R)-4-(2-amino-4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (3.0 g, 7.55 mmol) was initially charged in a 2:1:1 mixture of acetic acid/conc. hydrochloric acid/water (50 ml in total) at −10° C. A solution of sodium nitrite (547 mg, 7.93 mmol) in water (6 ml) was added, and the mixture was stirred at −10° C. for 15 min. This solution was then added to a suspension, pre-cooled to −10° C. and saturated with sulfur dioxide, of copper(I) chloride (75 mg, 755 μmol; 0.1 eq.) in glacial acetic acid (60 ml). The reaction was stirred at −10° C. (internal temperature) for 60 min and then slowly, over a period of 3 h, warmed to +15° C. (reaction monitored by HPLC and LC-MS). The reaction mixture was then once more cooled to 0° C., and then pipetted into about 300 ml of ice-cold water. The aqueous phase was extracted repeatedly with MTBE. The combined organic phases were washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The title compound was obtained as a solid (1.67 g, 73% pure according to LC-MS, 32% of theory) and used without further purification for subsequent reactions.

Workup

  1. customat −10° C
  2. additionThis solution was then added to a suspension
  3. stirringThe reaction was stirred at −10° C. (internal temperature) for 60 min
  4. waitslowly, over a period of 3 h
  5. temperaturewarmed to +15° C.
  6. custom(reaction monitored by HPLC and LC-MS)
  7. temperatureThe reaction mixture was then once more cooled to 0° C.
  8. extractionThe aqueous phase was extracted repeatedly with MTBE
  9. washThe combined organic phases were washed twice with saturated sodium chloride solution
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fc505d4b12a24eef8e2d65a367696a5e
Source dataset
uspto-grants-2014_04
Patent number
US08691817B2

Reaction notes

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