Hydrochloric Acid → 5-cyclopropyl-1H-benzo[c][1,2,6]thiadiazin-4-amine-2,2-dioxide

HRID 471561Notes

Reaction equation

HRID 471561 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]2[CH2:12][CH2:11]2)[C:3]=1[C:4]#[N:5].[S:13](Cl)(=[O:16])(=O)[NH2:14].[OH-:18].[Na+].Cl>CC(N(C)C)=O.O>[CH:10]1([C:6]2[C:3]3[C:4]([NH2:5])=[N:14][S:13](=[O:16])(=[O:18])[NH:1][C:2]=3[CH:9]=[CH:8][CH:7]=2)[CH2:11][CH2:12]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 24499Chlorosulfamic acidHCID 667472522-Amino-6-cyclopropylbenzonitrile

Product 1

HCID 674013605-cyclopropyl-1H-benzo[c][1,2,6]thiadiazin-4-amine-2,2-dioxideYield 28%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 2-amino-6-cyclopropylbenzonitrile (Example 92a) (1.0 eq., 626 μmol, 99 mg) and sulfamoyl chloride (1.5 eq., 939 μmol, 109 mg) in DMA (1 mL) was stirred in a scintillation vial at room temperature. After 2 hours, NaOH (1.5 eq., 939 μmol, 1N, 939 μL) and water (18 mL) were added and the resulting precipitated product stirred overnight at room temperature. The precipitate was filtered off and washed with water (3×5 mL). The wet precipitate was dissolved in EtOH (5 mL, 200 proof) and NaOH (2.5 eq., 1565 μmol, 1N, 1565 μL) was added. The reaction was heated to 80° C. with stirring overnight. The reaction mixture was cooled to room temperature and HCl (2.5 eq., 1565 μmol, 1N, 1565 μL) was added to the reaction vial. The ethanol and most of the water was removed on the rotary evaporator. The resulting precipitate was suspended in water (5 mL), stirred, filtered off, and washed with water (20 mL). The product was dried in a vacuum oven to give 5-cyclopropyl-1H-benzo[c][1,2,6]thiadiazin-4-amine-2,2-dioxide (41 mg, 28%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 0.71 (m, 2H), 1.04 (m, 2H), 2.401 (m, 1H), 6.85 (d, J=8 Hz, 2H), 7.37 (t+br. s, J=8 Hz, 2H), 8.40 (br. s, 1H), 10.80 (s, 1H). 1H NMR (400 MHz, CD3OD) δ 0.89 (m, 2H), 1.15 (m, 2H), 2.36 (m, 1H), 6.90 (d, J=8 Hz, 1H), 6.97 (d, J=8 Hz, 1H), 7.41 (t, J=8 Hz, 1H). MS 238 (MH+).

Workup

  1. customthe resulting precipitated product
  2. filtrationThe precipitate was filtered off
  3. washwashed with water (3×5 mL)
  4. dissolutionThe wet precipitate was dissolved in EtOH (5 mL, 200 proof)
  5. temperatureThe reaction was heated to 80° C.
  6. stirringwith stirring overnight
  7. temperatureThe reaction mixture was cooled to room temperature
  8. customThe ethanol and most of the water was removed on the rotary evaporator
  9. stirringstirred
  10. filtrationfiltered off
  11. washwashed with water (20 mL)
  12. customThe product was dried in a vacuum oven

Sources & evidence

ORD record
ord-0df5444f279348a681bbad5e1e8ee043
Source dataset
uspto-grants-2014_01
Patent number
US08633186B2

Reaction notes

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