Hydrochloric Acid → (S)-tert-butyl 3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidine-1-carboxylate

HRID 2280124Notes

Reaction equation

HRID 2280124 reaction equation
[NH2:1][C:2]1[C:3]([C:23]#[N:24])=[C:4]([CH:20]=[CH:21][CH:22]=1)[O:5][CH2:6][C@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]1.N1C=CC=CC=1.[S:31](Cl)(=[O:34])(=[O:33])[NH2:32].C([O-])(O)=O.[Na+].[OH-].[Na+].Cl>CC(N(C)C)=O.CCO.O>[NH2:24][C:23]1[C:3]2[C:4]([O:5][CH2:6][C@H:7]3[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[O:14])[CH2:8]3)=[CH:20][CH:21]=[CH:22][C:2]=2[NH:1][S:31](=[O:34])(=[O:33])[N:32]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 14798Sodium HydroxideHCID 24499Chlorosulfamic acidHCID 516892Sodium BicarbonateHCID 86714276(S)-tert-butyl 3-((3-amino-2-cyanophenoxy)methyl)piperidine-1-carboxylate

Product 1

HCID 86714275(S)-tert-butyl 3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of (S)-tert-butyl 3-((3-amino-2-cyanophenoxy)methyl)piperidine-1-carboxylate (Example 2c, 11.0 g, 33.2 mmol) in DMA (100 mL) was added pyridine (13.4 mL, 166 mmol) and sulfamoyl chloride (7.64 g, 66.4 mmol) in small portions. The mixture was stirred at room temperature under nitrogen for 1 hour until the reaction was complete according to LCMS. Saturated NaHCO3 was added until the mixture was neutral and the solution was extracted with EtOAc (3×). The combined organics were dried over Na2SO4 and concentrated. The residue was diluted with EtOH (100 mL) and NaOH (66.4 mL, 132.8 mmol, 2M solution) was added and the solution was heated to 80° C. for 3 hours. The reaction mixture was then allowed to cool to room temperature. The solution was further cool to 0° C. and neutralized with 2N HCl. Water was added and the desired product crashed out. The product was then filtered off and dried to yield the title compound (7.0 g, 51.4%). (M+H)-Boc=311.

Workup

  1. extractionthe solution was extracted with EtOAc (3×)
  2. dry with materialThe combined organics were dried over Na2SO4
  3. concentrationconcentrated
  4. additionwas added
  5. temperaturethe solution was heated to 80° C. for 3 hours
  6. temperatureto cool to room temperature

Sources & evidence

ORD record
ord-8e94cc8f5d1447d5b66c307d9ef0ca90
Source dataset
uspto-grants-2015_09
Patent number
US09138013B2

Reaction notes

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