Methyl iodide → HCID 58109280, compound

HRID 2037540Notes

Reaction equation

HRID 2037540 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@:20]([CH2:30][CH2:31][NH:32][C:33](=[O:35])[CH3:34])([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[O:19][C:18]2=[O:36])[CH3:16])=[CH:11][CH:10]=1.[H-].[Na+].I[CH3:40]>O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@:20]([CH2:30][CH2:31][N:32]([CH3:40])[C:33](=[O:35])[CH3:34])([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[O:19][C:18]2=[O:36])[CH3:16])=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 53473320HCID 53473320, compound

Product 1

HCID 58109280HCID 58109280, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-(2-((R)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)acetamide (60 mg, 0.121 mmol) in tetrahydrofuran anhydrous (5 mL) was added sodium hydride (15 mg, 0.605 mmol) at 0° C. and then stirred for 30 minutes at the same temperature. Iodomethane (86 mg, 0.605 mmol) was then added to the above mixture. The reaction mixture was stirred at rt for a further 8 h. The reaction mixture was poured into ice/water and extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and concentrated to afford the residue, which was purified by TLC and separated by preparative HPLC to give N-(2-((R)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)-N-methylacetamide (9 mg, 15%). LC-MS Method 3 tR=1.43, min, m/z=511; 1H NMR (CDCl3): 1.26 (m, 1H), 1.56 (m, 3H), 1.96 (m, 1H), 2.04 (m, 3H), 2.22 (m, 4H), 2.83 (m, 1H), 2.94 (m, 3H), 3.36 (m, 1H), 5.69 (m, 1H), 6.87 (m, 2H), 7.04 (m, 4H), 7.26 (m, 5H).

Workup

  1. stirringThe reaction mixture was stirred at rt for a further 8 h
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford the residue, which
  7. customwas purified by TLC
  8. customseparated by preparative HPLC

Sources & evidence

ORD record
ord-f086808905594e6d9c6108330f6c20cd
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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