Hydrochloric Acid → 3-Oxo-3,4-dihydro-2h-benzo[1,4]thiazine-6-sulfonic acid {3-[4-(6-methoxy-[1,5]naphthyridin-4-yl)-[1,2,3]triazol-1-yl]-propyl}amide

HRID 1767043Notes

Reaction equation

HRID 1767043 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[C:13]1[N:14]=[N:15][N:16]([CH2:18][CH2:19][CH2:20][N:21]2C(=O)C3C(=CC=CC=3)C2=O)[CH:17]=1.O.NN.Cl.C(N(CC)CC)C.[O:43]=[C:44]1[NH:49][C:48]2[CH:50]=[C:51]([S:54](Cl)(=[O:56])=[O:55])[CH:52]=[CH:53][C:47]=2[S:46][CH2:45]1>C(O)C.C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[C:13]1[N:14]=[N:15][N:16]([CH2:18][CH2:19][CH2:20][NH:21][S:54]([C:51]2[CH:52]=[CH:53][C:47]3[S:46][CH2:45][C:44](=[O:43])[NH:49][C:48]=3[CH:50]=2)(=[O:56])=[O:55])[CH:17]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)HCID 211131512-{3-[4-(6-Methoxy-[1,5]naphthyridin-4-yl)-[1,2,3]triazol-1-yl]-propyl)-isoindole-1,3-dioneHCID 218737563-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonyl chloride

Product 1

HCID 98064093-Oxo-3,4-dihydro-2h-benzo[1,4]thiazine-6-sulfonic acid {3-[4-(6-methoxy-[1,5]naphthyridin-4-yl)-[1,2,3]triazol-1-yl]-propyl}amideYield 29.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6212ChloroformSolvent2×

Procedure

To a suspension of 2-{3-[4-(6-Methoxy-[1,5]naphthyridin-4-yl)-[1,2,3]triazol-1-yl]-propyl)-isoindole-1,3-dione (180 mg, 0.43 mmole) in ethanol (3 mL) was added hydrazine hydrate (23 μL, 0.48 mmole) and the mixture was brought to reflux for 3 hours. After cooling 0.1 mL of 6N aqueous HCl was added to dissolve the product. The mixture was filtered and the filtrate was concentrated to dryness to afford the crude amine hydrochloride (85 mg). This material was suspended in chloroform (3 mL) and treated with triethylamine (0.18 mL, 1.3 mmole), followed by 3-oxo-3,4-dihydro-2H benzo[1,4]thiazine-6-sulfonyl chloride (100 mg, 0.4 mmole). After stirring 1 hour the mixture was diluted with chloroform, washed with saturated aqueous NaHCO3, dried (MgSO4), and chromatographed on silica (0–5% methanovchloroform) to provide the title compound as an off-white solid (60 mg, 27%). 1H NMR (400 MHz, DMSO-d6): 10.83 (br s, 1 H); 9.05 (s, 1 H); 8.84 (d, 1H); 8.37 (d, 1H); 8.29 (d, 1H); 7.85 (m, 1H); 7.46 (d, 1H); 7.24–7.42 (m, 3H); 4.60 (m, 2H); 4.17 (s, 3H); 3.53 (s, 2H); 2.80 (m, 2H); 2.14 (m, 2H). LC-MS (ES) m/e 512 (M+H)+.

Workup

  1. temperatureto reflux for 3 hours
  2. additionwas added
  3. dissolutionto dissolve the product
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate was concentrated to dryness
  6. customto afford the crude amine hydrochloride (85 mg)
  7. washwashed with saturated aqueous NaHCO3
  8. dry with materialdried (MgSO4)
  9. customchromatographed on silica (0–5% methanovchloroform)

Sources & evidence

ORD record
ord-4c73c418584f40c9be1ca10a3a9edaad
Source dataset
uspto-grants-2007_06
Patent number
US07232832B2

Reaction notes

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