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

HRID 711698Notes

Reaction equation

HRID 711698 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 mmol, 99 mg) and sulfamoyl chloride (1.5 eq., 939 mmol, 109 mg) in DMA (1 mL) was stirred in a scintillation vial at room temperature. After 2 hours, NaOH (1.5 eq., 939 mmol, 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 mmol, 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 mmol, 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-02ae4ce6f2ea4383b9422bf33274e707
Source dataset
uspto-grants-2015_11
Patent number
US09181276B2

Reaction notes

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