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Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → Ethyl (2S)-3-[3-({(3R)-N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-fluorophenyl]-2-methylpropanoate

HRID 626427
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HRID 626427 반응식
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:19]([OH:21])=O)[C@H:13]([C:15]([F:18])([F:17])[F:16])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([CH2:30][C@H:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:26]=[CH:27][C:28]=1[F:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.N1C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:19]([NH:22][C:23]1[CH:24]=[C:25]([CH2:30][C@H:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:26]=[CH:27][C:28]=1[F:29])=[O:21])[C@H:13]([C:15]([F:16])([F:17])[F:18])[CH3:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
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참가 물질

7

반응물 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58288322(+)-ethyl (2S)-3-(3-amino-4-fluorophenyl)-2-methylpropanoateHCID 118106631(3R)-N-[(Benzyloxy)carbonyl]-4,4,4-trifluorovaline

생성물 1

HCID 131735217Ethyl (2S)-3-[3-({(3R)-N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-fluorophenyl]-2-methylpropanoate

시약·촉매·용매

3
HCID 1049Pyridine용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

0.87 g (2.85 mmol) of (3R)—N-[(benzyloxy)carbonyl]-4,4,4-trifluorovaline (diastereomer mixture) and 0.77 g (3.42 mmol) of (+)-ethyl (2S)-3-(3-amino-4-fluorophenyl)-2-methylpropanoate were dissolved in a mixture of 5 ml of DMF and 2.5 ml of pyridine, and 1.41 g (3.71 mmol) of HATU were added at RT. The reaction mixture was stirred at RT overnight and then diluted with ethyl acetate. The mixture was washed successively with 1 N hydrochloric acid, sat. sodium bicarbonate solution and sat. sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1). This gave 1.27 g of the target product (87.2% of theory, diastereomer ratio about 4.8:1).

후처리

  1. additionwere added at RT
  2. washThe mixture was washed successively with 1 N hydrochloric acid, sat. sodium bicarbonate solution and sat. sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1)

출처 및 근거

ORD 기록
ord-8f7399f3a6444e13a02dbdc8dba35764
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09309198B2

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