Phosphorus sulfide (P2S5) → (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

HRID 1046110Notes

Reaction equation

HRID 1046110 reaction equation
[C:1]([NH:4][NH:5][C:6](=O)[C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]([N:15]2[CH2:20][CH2:19][C@:18]([CH2:28][CH:29]=[CH2:30])([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[O:17][C:16]2=[O:31])[CH3:14])=[CH:9][CH:8]=1)(=O)[CH3:2].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:34]>C1(C)C=CC=CC=1.N1C=CC=CC=1.CCOC(C)=O>[CH2:28]([C@@:18]1([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[O:17][C:16](=[O:31])[N:15]([C@H:13]([C:10]2[CH:11]=[CH:12][C:7]([C:6]3[S:34][C:1]([CH3:2])=[N:4][N:5]=3)=[CH:8][CH:9]=2)[CH3:14])[CH2:20][CH2:19]1)[CH:29]=[CH2:30]

Participants

5

Reactant 2

HCID 14817Phosphorus sulfide (P2S5)HCID 66857359N'-acetyl-4-((S)-1-((R)-6-allyl-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-3-yl)ethyl)benzohydrazide

Product 1

HCID 58109707(R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl)ethyl)-1,3-oxazinan-2-oneYield 61%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22007288Pyridine tolueneSolvent

Conditions

Temperature
130 °C

Procedure

N′-acetyl-4-((S)-1-((R)-6-allyl-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-3-yl)ethyl)benzohydrazide (4 mg, 0.009 mmol) was dissolved in 5:1 toluene/pyridine (1.5 mL). Phosphorus pentasulfide (8.1 mg, 2 equiv.) was added and the mixture was heated in Microwave Oven for 25 min at 130° C. LC-MS found reaction completed. The mixture was diluted with EtOAc (8 mL), washed with 5% HCl (2×5 mL), satd aq NaHCO3 solution (4 mL), brine (4 mL) and dried over Na2SO4. After filtration and concentration, the residue was purified by prep HPLC to afford 2.43 mg (61% yield). LC-MS Method 1 tR=1.7, min, m/z=438; 1H NMR (CDCl3) 7.66 (d, 2H), 7.26 (t, 2H), 7.02 (t, 2H), 6.97 (d, 2H), 5.69 (m, 2H), 5.07 (dd, 2H), 2.98 (m, 1H), 2.83 (s, 3H), 1.56 (d, 3H).

Workup

  1. customreaction
  2. washwashed with 5% HCl (2×5 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified by prep HPLC
  6. customto afford 2.43 mg (61% yield)

Sources & evidence

ORD record
ord-bbf23e15e7c449629b5c0bc77f6981db
Source dataset
uspto-grants-2013_10
Patent number
US08569292B2

Reaction notes

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