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}-1h-benzimidazole-2-sulfonamide

HRID 494623Notes

Reaction equation

HRID 494623 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.[N:39]1[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[NH:41][C:40]=1[S:48](Cl)(=[O:50])=[O:49]>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:48]([C:40]3[NH:39][C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=4[N:41]=3)(=[O:49])=[O:50])=[CH:4][C:5]=2[S:10](=[O:12])(=[O:11])[N:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 110638611H-Benzo[d]imidazole-2-sulfonyl 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 136384791n-{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}-1h-benzimidazole-2-sulfonamideYield 45%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of Example 39H (47.6 mg, 0.10 mmol), pyridine (64 mg, 0.80 mmol), and 2-benzimidazole sulfonyl chloride (87 mg, 0.40 mmol, prepared according to the procedure reported by S. M. Deshpande et al, J. Med. Chem. 1970,13, 143-144) in acetone (2 mL) was stirred at rt for 16 h. The reaction mixture was evaporated in vacuo and partitioned between ethyl acetate and water. 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 (28.0 mg, 45% yield). 1H NMR (300 MHz, DMSO-d6) δ 0.39 (m, 1H) 0.67 (d, J=6.62 Hz, 3H) 0.70 (d, J=6.62 Hz, 3H) 0.77 (m, 1H) 1.29 (m, 1H) 1.54 (s, 3H) 2.04 (m, 1H) 2.19 (m, 1H) 7.35 (dd, J=6.25, 2.94 Hz, 2H) 7.51 (m, 1H) 7.64 (m, 8H) 8.13 (d, J=7.72 Hz, 1H) 11.51 (s, 1H) 13.77 (s, 1H). MS (ESI+) m/z 620.0 (M+H)+, 641.9 (M+H−Na)+, (ESI−) m/z 618.0 (M−H)−.

Workup

  1. customThe reaction mixture was evaporated in vacuo
  2. custompartitioned between ethyl acetate and water
  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-5776d230ca294790b11bb83128a89f69
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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