Hydrochloric Acid → (S)-1-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy) methyl)piperidin-1-yl)butan-1-one

HRID 332937Notes

Reaction equation

HRID 332937 reaction equation
[S:1]([NH:5][C:6]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH2:15][C@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22](=[O:26])[CH2:23][CH2:24][CH3:25])[CH2:17]2)[C:7]=1[C:8]#[N:9])(=[O:4])(=[O:3])[NH2:2].[OH-].[Na+].Cl>CCO>[NH2:9][C:8]1[C:7]2[C:10]([O:14][CH2:15][C@H:16]3[CH2:21][CH2:20][CH2:19][N:18]([C:22](=[O:26])[CH2:23][CH2:24][CH3:25])[CH2:17]3)=[CH:11][CH:12]=[CH:13][C:6]=2[NH:5][S:1](=[O:3])(=[O:4])[N:2]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86714267(S)-2-sulfamoylamino-6-((1-butyrylpiperidin-3-yl)methoxy)benzonitrile

Product 1

HCID 86714266(S)-1-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy) methyl)piperidin-1-yl)butan-1-oneYield 63.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of (S)-2-sulfamoylamino-6-((1-butyrylpiperidin-3-yl)methoxy)benzonitrile (Example 1a, 9.5 g, 24.97 mmol) in EtOH (65 mL) was added at room temperature aq.NaOH (2.0 N, 37 mL, 74.91 mmol). The reaction mixture was refluxed for 4 hrs then cooled to 0° C. and neutralized carefully with 2N HCl. The precipitate was collected by filtration, re-crystallized from EtOH/H2O, and dried under vacuum to give the title compound as a white solid (6 g) in 63% yield. 1H NMR (400 MHz, DMSO-d6,) δ0.82-0.86 (m, 3H), 1.30-1.51 (m, 4H), 1.65 (m, 1H), 1.82 (m, 1H), 2.01-2.21 (m, 2H), 2.22-2.27 (m, 2H), 2.71-3.12 (m, 2H), 3.63-3.86 (m, 1H), 4.03 (m, 2H), 4.12 (m, 1H), 6.60 (m, 1H), 6.75 (t, J=8.0 Hz, 1H), 7.43-7.45 (m, 1H), 7.77 (d, J=20 Hz, 1H), 8.36 (m, 1H), 10.91 (s, 1H). MS 381 (MH+). Elem. Anal. Calcd.: C, 53.67%; H, 6.36%; N, 14.73%. Found: C, 53.64%; H, 6.63%; N, 14.73%

Workup

  1. temperatureThe reaction mixture was refluxed for 4 hrs
  2. filtrationThe precipitate was collected by filtration
  3. customre-crystallized from EtOH/H2O
  4. customdried under vacuum

Sources & evidence

ORD record
ord-6d9716b454034dc2bfa10a79ad6fb36d
Source dataset
uspto-grants-2014_11
Patent number
US08877922B2

Reaction notes

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