Phosgene → 2-(Chloromethyl)-N-[(4,6-dimethoxypyrimidin-2-yl)-aminocarbonyl]benzenesulfonamide

HRID 4137

Reaction equation

HRID 4137 reaction equation
[Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([NH:12][C:13]([NH:15][CH2:16]CCC)=[O:14])(=[O:11])=[O:10].C(Cl)(Cl)=O.ClCC1C=CC=CC=1S(N=C=O)(=O)=O.S(N=C=O)(N=C=O)(=O)=O.NC1[N:53]=[C:52]([O:54][CH3:55])[CH:51]=[C:50]([O:56][CH3:57])[N:49]=1>C1(C)C(C)=CC=CC=1.N12CCC(CC1)CN2.C(#N)C>[Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([NH:12][C:13]([NH:15][C:16]1[N:53]=[C:52]([O:54][CH3:55])[CH:51]=[C:50]([O:56][CH3:57])[N:49]=1)=[O:14])(=[O:10])=[O:11]

Participants

9

Reactant 5

HCID 6371PhosgeneHCID 77898Sulphonyl diisocyanateHCID 1189462-Amino-4,6-dimethoxypyrimidineHCID 136318872-(Chloromethyl)-N-(butylaminocarbonyl)benzenesulfonamideHCID 201526992-(Chloromethyl)benzenesulfonyl isocyanate

Product 1

HCID 133646172-(Chloromethyl)-N-[(4,6-dimethoxypyrimidin-2-yl)-aminocarbonyl]benzenesulfonamideYield 69.6%

Reagents, catalysts & solvents 3

HCID 136165Diazabicyclo(2.2.2)octaneCatalystHCID 6342AcetonitrileSolventHCID 7237O-XyleneSolvent

Procedure

A solution of 2-(chloromethyl)-N-(butylaminocarbonyl)benzene sulfonamide (1.33 g, 4.38 mmol) and diazabicyclo[2.2.2]octane (5 mg) in xylene (12 ml) was heated at reflux and contacted in portions with phosgene (1.0 ml. condensed phase). After 2.0 hrs at reflux, the mixture was cooled to room temperature, decanted, and volatiles were removed to give 1.56 g of crude product. The IR spectrum of 2-(chloromethyl)benzenesulfonyl isocyanate featured a strong band at 2250 cm-1. The crude sulfonyl isocyanate was contacted with acetonitrile (10 ml) and 2-amino-4,6-dimethoxypyrimidine (0.68 g, 4.4 mmol) and stirred for 16 hrs. Filtration gave 1.18 g of white solid, mp 192°-193°. The sample was dissolved in 0.5N NaOH, filtered and pH adjusted to 6.5. The mixture was cooled and filtered and the solid washed with ice water and dried to give 0.90 g of white solid. 1H nmr δDMSO-d6TMS 12.7 (brd s, 10.50 (s, 1H) 8.13-7.97 (m, 1H), 7.73-7.40 (m, 3H), 5.90 (s, 1H), 5.10 (s, 2H), 3.87 (s, 6H).

Workup

  1. temperatureat reflux
  2. temperatureAfter 2.0 hrs at reflux
  3. customdecanted
  4. customvolatiles were removed
  5. customto give 1.56 g of crude product
  6. filtrationFiltration

Sources & evidence

ORD record
ord-7101f12d796b4a7697ca6546a96de61b
Source dataset
uspto-grants-1988_02
Patent number
US04723990

Linked notes

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