Dicyclohexylcarbodiimide → HCID 86732191, compound

HRID 930369Notes

Reaction equation

HRID 930369 reaction equation
[NH2:1][C@@:2]([C:12]1[C:13]([F:19])=[N:14][CH:15]=[C:16]([Br:18])[CH:17]=1)([CH2:10][F:11])[CH2:3][C@H:4]([OH:9])[C:5]([F:8])([F:7])[F:6].[C:20]([N:28]=[C:29]=S)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C1(N=C=NC2CCCCC2)CCCCC1.C(N(C(C)C)CC)(C)C>CC#N.CCOC(C)=O.O>[Br:18][C:16]1[CH:17]=[C:12]([C@:2]2([CH2:10][F:11])[CH2:3][C@@H:4]([C:5]([F:6])([F:8])[F:7])[O:9][C:29]([NH:28][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:1]2)[C:13]([F:19])=[N:14][CH:15]=1

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 68284Benzoyl isothiocyanateHCID 81531DiisopropylethylamineHCID 86732190HCID 86732190, compound

Product 1

HCID 86732191HCID 86732191, compoundYield 58.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2S,4S)-4-amino-4-(5-bromo-2-fluoropyridin-3-yl)-1,1,1,5-tetrafluoropentan-2-ol (2.83 g, 8.11 mmol) in MeCN (70 mL) was added benzoyl isothiocyanate (1.20 ml, 8.92 mmol) and the mixture was stirred at room temperature for 1 h. N,N′-dicyclohexylcarbodiimide (1.840 g, 8.92 mmol) and diisopropylethylamine (2.82 ml, 16.21 mmol) were added. The mixture was stirred at 50° C. for 7 h. The reaction was worked up with water and EtOAc. The separated organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography using a gradient of 0-25% EtOAc/hexane to give N-((4S,6S)-4-(5-bromo-2-fluoropyridin-3-yl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (2.27 g, 4.75 mmol, 58.6% yield). MS m/z=479.8 [M+H]+. Calculated for C18H13BrF5N3O2: 478.2.

Workup

  1. stirringThe mixture was stirred at 50° C. for 7 h
  2. washThe separated organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-bbdd2d1e83284f80ac2517ebe6f5ef7c
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

Loading…