Pyridine → n-{3-[4-(2-Cyclopropylethyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-1,2,4-benzothiadiazin-7-yl}methanesulfonamide

HRID 494638Notes

Reaction equation

HRID 494638 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:29])[C:14]([CH2:24][CH2:25][CH:26]4[CH2:28][CH2:27]4)([CH3:23])[C:15]4[C:20]([C:21]=3[OH:22])=[CH:19][CH:18]=[CH:17][CH:16]=4)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.N1C=CC=CC=1.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>ClCCl>[CH:26]1([CH2:25][CH2:24][C:14]2([CH3:23])[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:21]([OH:22])=[C:12]([C:7]3[NH:6][C:5]4[CH:30]=[CH:31][C:2]([NH:1][S:39]([CH3:38])(=[O:41])=[O:40])=[CH:3][C:4]=4[S:9](=[O:11])(=[O:10])[N:8]=3)[C:13]2=[O:29])[CH2:28][CH2:27]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 1363848543-(7-Amino-1,1-dioxido-4h-1,2,4-benzothiadiazin-3-yl)-1-(2-cyclopropylethyl)-4-hydroxy-1-methylnaphthalen-2(1h)-one

Product 1

HCID 136384615n-{3-[4-(2-Cyclopropylethyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-1,2,4-benzothiadiazin-7-yl}methanesulfonamideYield 77.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of Example 158 (0.400 g, 0.914 mmol) and pyridine (0.591 mL, 7.312 mmol) in dichloromethane was added methanesulfonyl chloride (0.141 mL, 1.829 mmol) dropwise over 5 minutes and the resulting reaction mixture stirred for 12 hours. The solution was concentrated in. vacuo and purified by flash chromatography on SiO2 eluting with a 0-100% ethyl acetate/hexane gradient yielding the title compound (0.365 g, 77% yield) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6): δ ppm -0.22 (m, 2H) 0.24 (m, 2H) 0.85 (m, 2H) 1.57 (s, 3H) 2.14 (m, 1H) 2.32 (m, 1H) 3.08 (s, 3H) 7.56 (m, 4H) 7.73 (m, 4H) 8.14 (d, J=8.09 Hz, 1H) 10.23 (m, 1H) 13.79 (m, 1H). MS (ESI+) m/z=416 (M+H)+.

Workup

  1. customthe resulting reaction mixture
  2. concentrationThe solution was concentrated in
  3. customvacuo and purified by flash chromatography on SiO2 eluting with a 0-100% ethyl acetate/hexane

Sources & evidence

ORD record
ord-2f59a89b0b3747ac9b4b5d63c5f92125
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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