Sulfur Dioxide → 5-Cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfonyl chloride

HRID 2361909Notes

Reaction equation

HRID 2361909 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])[N:11]1[CH3:30].[ClH:31].O.N([O-])=O.[Na+].[S:37](=[O:39])=[O:38]>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:26])([F:27])[F:28])[CH:20]=3)[C:12](=[O:29])[N:11]2[CH3:30])=[C:2]([S:37]([Cl:31])(=[O:39])=[O:38])[CH:7]=1)#[N:9]

Participants

8

Reactant 4

HCID 1119Sulfur DioxideHCID 21885828Hydrate;hydrochlorideHCID 23668193Sodium NitriteHCID 66601757(4R)-4-(2-Amino-4-cyanophenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

Product 1

HCID 866507215-Cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfonyl chloride

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 176Acetic AcidSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Under argon, (4R)-4-(2-amino-4-cyanophenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (2.1 g, 5.1 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 (371 mg, 5.38 mmol) in water (2 ml) was slowly added dropwise, and the mixture was stirred at −10° C. to −5° C. for 40 min. This solution was then added to 45 ml of a suspension, pre-cooled to −10° C. and saturated with sulfur dioxide, of copper(I) chloride (101.4 mg, 1.0 mmol) in glacial acetic acid (44 ml). The mixture was stirred at 0° C. for about 30 min and then at +15° C. for 1 h (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 precipitate was filtered off and taken up in ethyl acetate (150 ml). The solution was 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 (2.13 g, 77% of theory, 92% pure) which was used without further purification for subsequent reactions.

Workup

  1. customat −10° C
  2. stirringThe mixture was stirred at 0° C. for about 30 min
  3. customat +15° C. for 1 h (reaction monitored by HPLC and LC-MS)
  4. filtrationThe precipitate was filtered off
  5. washThe solution was washed twice with saturated sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2fa749d38d5b4413bbe66addb487e5e6
Source dataset
uspto-grants-2014_04
Patent number
US08691817B2

Reaction notes

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