Methanol → tert-Butyl (3R)-3-[{[2,2-dimethyl-3-oxo-4-[2-(propanethioylamino)ethyl]-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylate

HRID 1942465Notes

Reaction equation

HRID 1942465 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[C:9]2[CH:10]=[C:11]([C:18]([N:20]([CH:34]([CH3:36])[CH3:35])[C@@H:21]3[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]3)=[O:19])[C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=2[O:7][C:6]([CH3:38])([CH3:37])[C:5]1=[O:39].[S:40](S(O)(=O)=O)(O)(=O)=O.[CH3:48][CH2:49][CH2:50]C.C(N(CC)CC)C.CO>O>[CH3:38][C:6]1([CH3:37])[C:5](=[O:39])[N:4]([CH2:3][CH2:2][NH:1][C:50](=[S:40])[CH2:49][CH3:48])[C:9]2[CH:10]=[C:11]([C:18]([N:20]([CH:34]([CH3:35])[CH3:36])[C@@H:21]3[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[CH2:22]3)=[O:19])[C:12]([C:14]([F:15])([F:17])[F:16])=[CH:13][C:8]=2[O:7]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 58376011tert-butyl (3R)-3-[{[4-(2-aminoethyl)-2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylateHCID 86656349Methylpropane dithionate

Product 1

HCID 86656348tert-Butyl (3R)-3-[{[2,2-dimethyl-3-oxo-4-[2-(propanethioylamino)ethyl]-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylateYield 137.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To tert-butyl (3R)-3-[{[4-(2-aminoethyl)-2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylate (100 mg) were added methylpropane dithionate (23 mg), triethylamine (0.050 ml) and MeOH (3 ml), and the mixture was stirred at room temperature for 3 hours. After the reaction was complete, water was added to the reaction solution, and the mixture was extracted with ethyl acetate solution. The obtained ethyl acetate solution was washed with water and an aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2) to give the title compound (90 mg) as a colorless liquid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate solution
  2. washThe obtained ethyl acetate solution was washed with water
  3. dry with materialan aqueous sodium chloride solution, dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-7e6fb9c52ab648ff99f9b120481e8176
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

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