Benzoyl isothiocyanate → HCID 86732168, compound

HRID 930348Notes

Reaction equation

HRID 930348 reaction equation
[NH2:1][C@@:2]([C:12]1[C:17]([F:18])=[CH:16][CH:15]=[C:14]([Br:19])[N:13]=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.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.C([O-])(O)=O.[Na+]>CC#N>[Br:19][C:14]1[N:13]=[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:17]([F:18])=[CH:16][CH:15]=1

Participants

7

Reactant 5

HCID 68284Benzoyl isothiocyanateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86732166HCID 86732166, compound

Product 1

HCID 86732168HCID 86732168, compoundYield 82.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a 150 mL round-bottomed flask was added (2S,4S)-4-amino-4-(6-bromo-3-fluoropyridin-2-yl)-1,1,1,5-tetrafluoropentan-2-ol (1.54 g, 4.41 mmol), MeCN (30 mL) and benzoyl isothiocyanate (Aldrich; 0.712 mL, 5.29 mmol). The reaction mixture was stirred at rt for 45 min and then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (Oakwook Products, Inc.; 1.015 g, 5.29 mmol) and N,N-diisopropylethylamine (Aldrich; 1.54 mL, 8.82 mmol) were added. The solution was stirred at rt for 2 h and then treated with sat NaHCO3 and extracted with EtOAc (2×100 mL). The combined extracts were washed with water (1×100 mL) and brine and then dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (Gradient: 0.0 to 20% EtOAc/hexane) afforded N-((4S,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (1.74 g, 3.64 mmol, 82% yield) as an off-white foam. MS m/z=480.0 [M+H]+. Calculated for C18H13BrF5N3O2: 479.0.

Workup

  1. stirringThe solution was stirred at rt for 2 h
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe combined extracts were washed with water (1×100 mL) and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated onto silica
  6. customPurification by silica gel chromatography (Gradient: 0.0 to 20% EtOAc/hexane)

Sources & evidence

ORD record
ord-d107a4f7a9e64fb6a8d48b7491891c17
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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