Methanol → N-[(4aR,7aR)-7a-(5-cyanothiophen-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 338138Notes

Reaction equation

HRID 338138 reaction equation
[C:1]([NH:9][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:18][N:17](C(OCC3C=CC=CC=3)=O)[CH2:16][C@:14]2([C:29]2[S:30][C:31]([C:34]#[N:35])=[CH:32][CH:33]=2)[N:15]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO>C(#N)C.I[Si](C)(C)C>[C:34]([C:31]1[S:30][C:29]([C@:14]23[CH2:16][NH:17][CH2:18][C@H:13]2[CH2:12][S:11][C:10]([NH:9][C:1](=[O:8])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[N:15]3)=[CH:33][CH:32]=1)#[N:35]

Participants

5

Reactant 2

HCID 887MethanolHCID 86762221Benzyl(4aR,7aR)-2-(benzoylamino)-7a-(5-cyanothiophen-2-yl)-4a,5,7,7a-tetrahydropyrrolo[3,4-d][1,3]thiazine-6(4H)-carboxylate

Product 1

HCID 86762239N-[(4aR,7aR)-7a-(5-cyanothiophen-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamideYield 118%

Reagents, catalysts & solvents 2

HCID 85247Trimethylsilyl iodideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a stirred clear and colorless solution of the benzyl (4aR,7aR)-2-(benzoylamino)-7a-(5-cyanothiophen-2-yl)-4a,5,7,7a-tetrahydropyrrolo[3,4-d][1,3]thiazine-6(4H)-carboxylate (405 mg, 0.806 mmol) in acetonitrile (16 mL) under an atmosphere of nitrogen at room temperature is added iodotrimethylsilane (345 μL, 2.42 μmol). The resulting pale yellow solution is stirred at room temperature for 70 minutes. Methanol (391 μL, 9.67 mmol) is added and the pale yellow mixture is stirred for 5 minutes, and then concentrated under reduced pressure. The residue is partially purified by silica gel chromatography, eluting with a dichloromethane/methanol, gradient from 99:1 to 90:10, to give the title compound (349 mg, 118%) as a pale yellow solid (assume quantitative recovery and carry partially purified material into next step). MS/ES (m/z) 369.0 (M+H).

Workup

  1. stirringthe pale yellow mixture is stirred for 5 minutes
  2. concentrationconcentrated under reduced pressure
  3. customThe residue is partially purified by silica gel chromatography
  4. washeluting with a dichloromethane/methanol, gradient from 99:1 to 90:10

Sources & evidence

ORD record
ord-26fbc79dbce74a2d821e19cc8ab765b0
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

Loading…