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}ethanesulfonamide

HRID 2224935Notes

Reaction equation

HRID 2224935 reaction equation
[CH2:1]([S:3](Cl)(=[O:5])=[O:4])[CH3:2].Cl.[NH2:8][C:9]1[CH:38]=[CH:37][C:12]2[NH:13][C:14]([C:19]3[C:20](=[O:36])[C@:21]([CH3:35])([CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])[C:22]4[C:27]([C:28]=3[OH:29])=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:15][S:16](=[O:18])(=[O:17])[C:11]=2[CH:10]=1.N1C=CC=CC=1>CC(C)=O>[OH:29][C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C@@:21]([CH3:35])([CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])[C:20](=[O:36])[C:19]=1[C:14]1[NH:13][C:12]2[CH:37]=[CH:38][C:9]([NH:8][S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[CH:10][C:11]=2[S:16](=[O:18])(=[O:17])[N:15]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 11667Ethanesulfonyl 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 136384653n-{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}ethanesulfonamideYield 95%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Ethane sulfonylchloride (75.6 mg, 0.588 mmol) was added carefully dropwise to a solution of Example 39H (70.0 mg, 0.147 mmol) and pyridine (93.1 mg, 1.18 mmol) in acetone (7 mL). The reaction mixture was stirred for 4 h and then concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic phase was dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with a 0-25% ethyl acetate/hexane gradient to give the title compound (74 mg, 95%). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.42 m, 1 H) 0.69 (d, J=6.62 Hz, 3H) 0.72 (d, J=6.62 Hz, 3 H) 0.80 m, 1 H) 1.22 (t, J=7.35 Hz, 3 H) 1.33 (m, 1 H) 1.57 (s, 3 H) 2.07 m, 1 H) 2.22 m, 1 H) 3.19 m, 2 H) 5.76 (s, 1 H) 7.53 (dd, J=7.91, 4.23 Hz, 1H) 7.57 (dd, J=8.82, 2.21 Hz, 1 H) 7.63 (d, J=2.21 Hz, 1 H) 7.71 (d, J=8.82 Hz, 1 H) 7.76 (d, J=3.68 Hz, 2 H) 8.16 (d, J=7.72 Hz, 1 H) 10.31 (s, 1 H) 13.77 (s, 1 H).). MS (ESI+) m/z 532.0 (M+H)+, 549.1 (M+NH4)+ (ESI−) m/z 530.1 (M−H)−.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on silica gel
  7. washeluting with a 0-25% ethyl acetate/hexane gradient

Sources & evidence

ORD record
ord-a741606a841f48f9b73ff32effb8381c
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

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