Pyridine → A-837093

HRID 494556Notes

Reaction equation

HRID 494556 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.[S:33](Cl)([CH3:36])(=[O:35])=[O:34].N1C=CC=CC=1>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:33]([CH3:36])(=[O:35])=[O:34])=[CH:4][C:5]=2[S:10](=[O:12])(=[O:11])[N:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl 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 135436761A-837093Yield 90.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of Example 39H (2.76 g, 5.80 mmol), mesyl chloride (1.79 mL, 23.2 mmol), and pyridine (3.75 mL, 46.4 mmol) in acetone (80 mL) was stirred at 25° C. for 18 hours. The solution was partitioned between ethyl acetate and dilute citric acid and the layers were separated. The ethyl acetate layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with methylene chloride and 2.5% methanol in methylene chloride to give the desired product (2.71 g, 90%). 1H NMR (300 MHz, DMSO-d6): δ ppm 0.43 (m, 1 H) 0.74 (m, 7 H) 1.34 (m, 1 H) 1.57 (m, 3 H) 2.15 (m, 2 H) 3.08 (m, 3 H) 7.56 (m, 3 H) 7.75 (m, 3 H) 8.16 (m, 1 H) 10.26 (m, 1 H) 13.76 (m, 1 H).

Workup

  1. customThe solution was partitioned between ethyl acetate and dilute citric acid
  2. customthe layers were separated
  3. dry with materialThe ethyl acetate layer was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel eluting with methylene chloride and 2.5% methanol in methylene chloride

Sources & evidence

ORD record
ord-1b65eaec37c04711968ddac9411d94b4
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

Loading…