Pyridine → n-{6-[({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}amino)sulfonyl]-2-naphthyl}acetamide

HRID 2224939Notes

Reaction equation

HRID 2224939 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.[C:39]([NH:42][C:43]1[CH:44]=[C:45]2[C:50](=[CH:51][CH:52]=1)[CH:49]=[C:48]([S:53](Cl)(=[O:55])=[O:54])[CH:47]=[CH:46]2)(=[O:41])[CH3:40]>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:53]([C:48]3[CH:49]=[C:50]4[C:45](=[CH:46][CH:47]=3)[CH:44]=[C:43]([NH:42][C:39](=[O:41])[CH3:40])[CH:52]=[CH:51]4)(=[O:55])=[O:54])=[CH:4][C:5]=2[S:10](=[O:12])(=[O:11])[N:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 1198272-Naphthalenesulfonyl chloride, 6-(acetylamino)-HCID 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 136384631n-{6-[({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}amino)sulfonyl]-2-naphthyl}acetamideYield 61%

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 6-acetylamino-2-naphthalenesulfonyl chloride (56.7 mg, 0.20 mmol, prepared by the procedure as described in J. Med. Chem., 1995, 38, 8, p. 1344-1354) 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 99:1 dichloromethane/methanol to provide the title compound (20.8 mg, 61% yield). 1H NMR (300 MHz, DMSO-d6) δ 0.38 m, 1 H) 0.66 (d, J=7.35 Hz, 3 H) 0.68 (d, J=6.99 Hz, 3H) 0.80 m, 1 H) 1.30 m, 1 H) 1.53 (s, 3 H) 2.02 m, 1 H) 2.10 (s, 3 H) 2.18 (m, 1 H) 7.52 m, 4 H) 7.69 m, 4 H) 7.99 (d, J=8.82 Hz, 1 H) 8.07 (d, J=8.82 Hz, 1 H) 8.11 (d, J=8.09 Hz, 1H) 8.38 (s, 2 H) 10.32 (s, 1 H) 10.87 (s, 1 H) 13.72 (s, 1 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 99:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-e4eaa3693d324abd81e254526fe60235
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

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