Pyridine → Methanesulfonamide, N-(3-((4R)-4-(3,3-dimethylbutyl)-3,4-dihydro-1-hydroxy-4-methyl-3-oxo-2-naphthalenyl)-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl)-

HRID 494598Notes

Reaction equation

HRID 494598 reaction equation
[NH2:1][C:2]1[CH:32]=[CH:31][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:30])[C@@:14]([CH2:24][CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])([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.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>ClCCl>[CH3:29][C:26]([CH3:27])([CH3:28])[CH2:25][CH2:24][C@:14]1([CH3:23])[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:21]([OH:22])=[C:12]([C:7]2[NH:6][C:5]3[CH:31]=[CH:32][C:2]([NH:1][S:40]([CH3:39])(=[O:42])=[O:41])=[CH:3][C:4]=3[S:9](=[O:11])(=[O:10])[N:8]=2)[C:13]1=[O:30]

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 135869465(1R)-3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-1-(3,3-dimethylbutyl)-4-hydroxy-1-methylnaphthalen-2(1H)-one

Product 1

HCID 135430231Methanesulfonamide, N-(3-((4R)-4-(3,3-dimethylbutyl)-3,4-dihydro-1-hydroxy-4-methyl-3-oxo-2-naphthalenyl)-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl)-Yield 87.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Example 49-6 (235.0 g, 0.518 mol) and pyridine (123.0 g, 1.55 mol) in dichloromethane (1645 mL) at 18-20° C. was added methane sulfonyl chloride (89.0 g, 0.777 mol) over 45 minutes. The solution was mixed at RT for 3.5 h then quenched with 1 M HCl (1500 mL). The layers were separated and the organic layer was concentrated under vacuum. The product was crystallized from ethyl acetate/heptane (1/1, 8 volumes) to give the title compound (240.01 g, 87%).

Workup

  1. additionThe solution was mixed at RT for 3.5 h
  2. customthen quenched with 1 M HCl (1500 mL)
  3. customThe layers were separated
  4. concentrationthe organic layer was concentrated under vacuum
  5. customThe product was crystallized from ethyl acetate/heptane (1/1, 8 volumes)

Sources & evidence

ORD record
ord-d948df74791f4d48a6eb68fe6b465990
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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