Triphosgene → (5R)-5-ethyl-5-methyl-3-[6-[(2,4,4-trimethyl-3,1-benzoxazin-5-yl)oxy]-3-pyridyl]imidazolidine-2,4-dione

HRID 527716노트

반응식

HRID 527716 반응식
[NH2:1][C@:2]([CH3:28])([CH2:26][CH3:27])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([O:12][C:13]2[C:18]3[C:19]([CH3:25])([CH3:24])[O:20][C:21]([CH3:23])=[N:22][C:17]=3[CH:16]=[CH:15][CH:14]=2)=[CH:10][CH:11]=1)=[O:4].Cl[C:30](Cl)([O:32]C(=O)OC(Cl)(Cl)Cl)Cl>C(OCC)(=O)C.O>[CH2:26]([C@@:2]1([CH3:28])[NH:1][C:30](=[O:32])[N:5]([C:6]2[CH:7]=[N:8][C:9]([O:12][C:13]3[C:18]4[C:19]([CH3:25])([CH3:24])[O:20][C:21]([CH3:23])=[N:22][C:17]=4[CH:16]=[CH:15][CH:14]=3)=[CH:10][CH:11]=2)[C:3]1=[O:4])[CH3:27]

참가 물질

5

반응물 2

HCID 94429TriphosgeneHCID 67959970(2R)-2-amino-2-methyl-N-[6-[(2,4,4-trimethyl-3,1-benzoxazin-5-yl)oxy]-3-pyridyl]butanamide2회

생성물 1

HCID 57411185(5R)-5-ethyl-5-methyl-3-[6-[(2,4,4-trimethyl-3,1-benzoxazin-5-yl)oxy]-3-pyridyl]imidazolidine-2,4-dione수율 187.7%

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매3회

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온도
0 °C

실험 절차

To a solution of (2R)-2-amino-2-methyl-N-[6-[(2,4,4-trimethyl-3,1-benzoxazin-5-yl)oxy]-3-pyridyl]butanamide (Intermediate 205, 143 mg, 0.37 mmol) and TEA (0.21 mL) in ethyl acetate (2.5 mL) at 0° C., triphosgene (44 mg, 0.15 mmol) dissolved in ethyl acetate (2.5 mL) was added drop wise in 10 min. The reaction mixture was stirred at 0° C. for 40 min. The reaction mixture was diluted with water (5 mL) and ethyl acetate (10 mL). Phases were separated and the aqueous was back-extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated and the residue was purified by flash chromatography on silica gel using ethyl acetate as eluent affording the title compound (115 mg) as white solid.

후처리

  1. additionwas added drop wise in 10 min
  2. customPhases were separated
  3. extractionthe aqueous was back-extracted with ethyl acetate (2×10 mL)
  4. washThe combined organic layers were washed with brine (15 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by flash chromatography on silica gel

출처 및 근거

ORD 기록
ord-f2c74c2b39124f288bb3fae07153c34c
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346790B2

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