(4R)-2-[bis(methylthio)methylene]-4-(3,3-dimethylbutyl)-4-methylnaphthalene-1,3(2H,4H)-dione → (1R)-1-(3,3-dimethylbutyl)-4-hydroxy-3-{7-[(methoxymethoxy)methyl]-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl}-1-methylnaphthalen-2(1H)-one

HRID 2224989Notes

Reaction equation

HRID 2224989 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:11][O:12][CH2:13][O:14][CH3:15])[C:6]=1[S:7]([NH2:10])(=[O:9])=[O:8].CS[C:18](SC)=[C:19]1[C:28](=[O:29])[C@@:27]([CH2:31][CH2:32][C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:30])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]1=[O:37]>C1(C)C=CC=CC=1>[CH3:34][C:33]([CH3:36])([CH3:35])[CH2:32][CH2:31][C@:27]1([CH3:30])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([OH:37])=[C:19]([C:18]2[NH:1][C:2]3[S:3][CH:4]=[C:5]([CH2:11][O:12][CH2:13][O:14][CH3:15])[C:6]=3[S:7](=[O:8])(=[O:9])[N:10]=2)[C:28]1=[O:29]

Participants

4

Reactant 2

HCID 11152684(4R)-2-[bis(methylthio)methylene]-4-(3,3-dimethylbutyl)-4-methylnaphthalene-1,3(2H,4H)-dioneHCID 574551872-Amino-4-[(methoxymethoxy)methyl]-3-thiophenesulfonamide

Product 1

HCID 135903311(1R)-1-(3,3-dimethylbutyl)-4-hydroxy-3-{7-[(methoxymethoxy)methyl]-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl}-1-methylnaphthalen-2(1H)-oneYield 85%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of the product of Example 10E (2.02 g, 7.9 mmol) and the product of Example 49E (2.49 g, 6.9 mmol) in 200 mL of toluene was warmed to reflux for 5 h, cooled, and concentrated in vacuo. The crude material was chromatographed on silica gel with methanol/dichloromethane (1:99) to afford the title compound (3.03 g, 85% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.39 (td, J=12.59, 3.13 Hz, 1 H) 0.72 (s, 9 H) 0.82 (m, 1 H) 1.57 (s, 3 H) 2.04 (m, 1 H) 2.22 (td, J=12.69, 4.41 Hz, 1 H) 3.33 (s, 3 H) 4.63 (s, 2 H) 4.71 (s, 2 H) 7.40 (s, 1 H) 7.53 (m, 1 H) 7.74 (d, J=4.04 Hz, 2 H) 8.13 (d, J=7.72 Hz, 1 H) 14.00 (s, 1 H); MS (APCI−) m/z 517 (M−H)−; Analysis calc'd for (C25H30N2O6S2): C, 57.89; H, 5.83; N, 5.40. Found: C, 57.82; H, 6.12; N, 5.05.

Workup

  1. temperatureto reflux for 5 h
  2. temperaturecooled
  3. concentrationconcentrated in vacuo
  4. customThe crude material was chromatographed on silica gel with methanol/dichloromethane (1:99)

Sources & evidence

ORD record
ord-52b2ced3adac45e5b06cd3ae1da8f388
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

Loading…