Pyridine → n-{3-[(4r)-1-Hydroxy-4-methyl-4-(3-methylbutyl)-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-1,2,4-benzothiadiazin-7-yl}naphthalene-2-sulfonamide

HRID 2224937Notes

Reaction equation

HRID 2224937 reaction equation
Cl.[NH2:2][C:3]1[CH:32]=[CH:31][C:6]2[NH:7][C:8]([C:13]3[C:14](=[O:30])[C@:15]([CH3:29])([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[C:16]4[C:21]([C:22]=3[OH:23])=[CH:20][CH:19]=[CH:18][CH:17]=4)=[N:9][S:10](=[O:12])(=[O:11])[C:5]=2[CH:4]=1.N1C=CC=CC=1.[CH:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:42]=[CH:41][C:40]=1[S:49](Cl)(=[O:51])=[O:50]>CC(C)=O>[OH:23][C:22]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C@@:15]([CH3:29])([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[C:14](=[O:30])[C:13]=1[C:8]1[NH:7][C:6]2[CH:31]=[CH:32][C:3]([NH:2][S:49]([C:40]3[CH:41]=[CH:42][C:43]4[C:48](=[CH:47][CH:46]=[CH:45][CH:44]=4)[CH:39]=3)(=[O:51])=[O:50])=[CH:4][C:5]=2[S:10](=[O:12])(=[O:11])[N:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 71252-Naphthalenesulfonyl chlorideHCID 135869462(1R)-3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-methyl-1-(3-methylbutyl)naphthalen-2(1 H)-one hydrochloride

Product 1

HCID 136384730n-{3-[(4r)-1-Hydroxy-4-methyl-4-(3-methylbutyl)-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-1,2,4-benzothiadiazin-7-yl}naphthalene-2-sulfonamideYield 39.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of Example 39H (23.8 mg, 0.050 mmol), pyridine (31.6 mg, 0.40 mmol), and 2-naphthalenesulfonyl chloride (45.3 mg, 0.20 mmol) in acetone (1.5 mL) was stirred at rt for 18 h. The reaction mixture was evaporated in vacuo and partitioned between ethyl acetate and 1 N HCl. The organic phase was separated, dried (MgSO4), filtered, and evaporated in vacuo. The residue was purified by chromatography on silica gel eluting with 4:1 hexane/ethyl acetate to provide the title compound (12.3 mg, 39% yield). 1H NMR (300 MHz, DMSO-d6) 8 ppm 0.37 m, 1 H) 0.66 (d, J=6.62 Hz, 3 H) 0.68 (d, J=6.62 Hz, 3 H) 0.77 m, 1 H) 1.29 m, 1 H) 1.52 (s, 3 H) 2.02 m, 1 H) 2.18 m, 1 H) 7.52 (m, 4 H) 7.68 m, 2 H) 7.73 (d, J=4.04 Hz, 2 H) 7.79 (dd, J=8.46, 1.84 Hz, 1 H) 8.01 (d, J=7.72 Hz, 1 H) 8.13 (m, 3H) 8.50 (s, 1 H) 10.93 (s, 1 H) 13.71 (s, 1 H). MS (ESI+) m/z 630.0 (M+H)+, 647.1 (M+NH4)+, (ESI−) m/z 628.1 (M−H)−.

Workup

  1. customThe reaction mixture was evaporated in vacuo
  2. custompartitioned between ethyl acetate and 1 N HCl
  3. customThe organic phase was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by chromatography on silica gel eluting with 4:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-222a284353be403d8fd248e20d12e5b4
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

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