Cyclohexyl isocyanate → 1-Cyclohexyl-3-(5-ethoxy-2,2-dioxido-1,2,3-benzoxathiazin-4-yl)urea

HRID 1920715Notes

Reaction equation

HRID 1920715 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([O:12][CH2:13][CH3:14])=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][S:4](=[O:16])(=[O:15])[N:3]=1.[CH:17]1([N:23]=[C:24]=[O:25])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH:17]1([NH:23][C:24]([NH:1][C:2]2[C:7]3[C:8]([O:12][CH2:13][CH3:14])=[CH:9][CH:10]=[CH:11][C:6]=3[O:5][S:4](=[O:16])(=[O:15])[N:3]=2)=[O:25])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 18502Cyclohexyl isocyanateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 462386994-Amino-5-ethoxy-1,2,3-benzoxathiazine 2,2-dioxide

Product 1

HCID 582677001-Cyclohexyl-3-(5-ethoxy-2,2-dioxido-1,2,3-benzoxathiazin-4-yl)urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

0.15 g (0.61 mmol) of 4-amino-5-ethoxy-1,2,3-benzoxathiazine 2,2-dioxide is stirred with 0.1 g (0.79 mmol) of cyclohexyl isocyanate in 30 ml of dry tetrahydrofuran in the presence of 10 mg of DBU, first at room temperature for 1 hour and then at 40° C. for 18 hours. The mixture is concentrated under reduced pressure, and the residue is dissolved in dichloromethane and washed with water. The organic phase is dried over magnesium sulphate and concentrated under reduced pressure. This gives 0.15 g of crude product which, after dissolution in 14 ml of acetonitrile and 6 ml of water, is purified by means of reversed phase HPLC (Kromasil 100 C18, 250×40 mm, 5 μm, 0.01% HCOOH/H2O acetonitrile gradient 34/66, isocratic). This gives 55 mg (24.2% of theory) of compound I-24 as a white solid.

Workup

  1. concentrationThe mixture is concentrated under reduced pressure
  2. dissolutionthe residue is dissolved in dichloromethane
  3. washwashed with water
  4. dry with materialThe organic phase is dried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThis gives 0.15 g of crude product which, after dissolution in 14 ml of acetonitrile
  7. custom6 ml of water, is purified by means of reversed phase HPLC (Kromasil 100 C18, 250×40 mm, 5 μm, 0.01% HCOOH/H2O acetonitrile gradient 34/66, isocratic)

Sources & evidence

ORD record
ord-c21553c49bd8489e864dfc9c1ea145c0
Source dataset
uspto-grants-2012_05
Patent number
US08173641B2

Reaction notes

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