Hydrochloric Acid → 1-benzyl-3-(7-bromo-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1,8-naphthyridin-2(1H)-one

HRID 601125Notes

Reaction equation

HRID 601125 reaction equation
[NH2:1][S:2]([C:5]1[CH:10]=[C:9]([Br:11])[CH:8]=[CH:7][C:6]=1[NH:12][C:13]([C:15]1[C:16](=[O:33])[N:17]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:18]2[C:23]([C:24]=1[OH:25])=[CH:22][CH:21]=[CH:20][N:19]=2)=O)(=[O:4])=[O:3].Cl>[OH-].[K+]>[CH2:26]([N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][N:19]=2)[C:24]([OH:25])=[C:15]([C:13]2[NH:12][C:6]3[CH:7]=[CH:8][C:9]([Br:11])=[CH:10][C:5]=3[S:2](=[O:4])(=[O:3])[N:1]=2)[C:16]1=[O:33])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67063612N-[2-(aminosulfonyl)-4-bromophenyl]-1-benzyl-4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide

Product 1

HCID 1355073191-benzyl-3-(7-bromo-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1,8-naphthyridin-2(1H)-oneYield 84%

Reagents, catalysts & solvents 1

HCID 14797Potassium HydroxideSolvent

Procedure

A mixture of the product of Example 84C (0.074 g, 0.14 mmol) in aqueous potassium hydroxide (10%, 5 mL) was heated to reflux for 16 hours, cooled to room temperature and adjusted to pH 3 with 6 M HCl. The mixture was filtered and the filter cake was washed with water, triturated with tetrahydrofuran/water, filtered, and dried under vacuum to give the title compound (0.060 g, 84%). MS (ESI+) m/z 511.0 (M+H)+, 512.9 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 5.62 (s, 2H), 7.21 (m, 1H), 7.27 (m, J=4.41 Hz, 5H), 7.36 (m, 1H), 7.50 (d, J=8.82 Hz, 1H), 7.84 (dd, J=8.82, 1.84 Hz, 1H), 7.95 (s, 1H), 8.51 (dd, J=7.91, 1.65 Hz, 1H), 8.68 (m, 1H). The sodium salt of the title compound was prepared according to the procedure of Example 1D. MS (ESI+) m/z 511.0 (M+H−Na)+, 512.9 (M+H−Na)+; 1H NMR (300 MHz, DMSO-d6) δ 5.52 (s, 2H), 7.17 (m, 2H), 7.24 (m, 5H), 7.71 (m, 1H), 7.76 (d, J=2.21 Hz, 1H), 8.40 (dd, J=7.72, 1.84 Hz, 1H), 8.49 (dd, J=4.60, 2.02 Hz, 1H), 16.09 (s, 1H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 hours
  3. filtrationThe mixture was filtered
  4. washthe filter cake was washed with water
  5. customtriturated with tetrahydrofuran/water
  6. filtrationfiltered
  7. customdried under vacuum

Sources & evidence

ORD record
ord-96ebf0d053a94df181f6af8c2f64f574
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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