Methyl iodide → HCID 58109280, 화합물

HRID 2037540노트

반응식

HRID 2037540 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

HCID 58109280HCID 58109280, 화합물수율 15%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f086808905594e6d9c6108330f6c20cd
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575156B2

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