Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 3-(3,5-Difluoro-phenyl)-2-[(2-isoquinolin-3-yl-1h-benzoimidazole-4-carbonyl)-amino]-propionic acid methyl ester

HRID 1910113노트

반응식

HRID 1910113 반응식
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][CH:18]=[C:19]([C:20](O)=[O:21])[C:13]=3[N:12]=2)[N:2]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:48][O:49][C:50](=[O:62])[CH:51]([NH2:61])[CH2:52][C:53]1[CH:58]=[C:57]([F:59])[CH:56]=[C:55]([F:60])[CH:54]=1>C(OCC)(=O)C>[CH3:48][O:49][C:50](=[O:62])[CH:51]([NH:61][C:20]([C:19]1[C:13]2[N:12]=[C:11]([C:3]3[N:2]=[CH:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)[NH:15][C:14]=2[CH:16]=[CH:17][CH:18]=1)=[O:21])[CH2:52][C:53]1[CH:54]=[C:55]([F:60])[CH:56]=[C:57]([F:59])[CH:58]=1

참가 물질

5

반응물 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66940454Methyl 2-amino-3-(3,5-difluorophenyl)propanoate hydrochlorideHCID 669406062-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid

생성물 1

HCID 669403573-(3,5-Difluoro-phenyl)-2-[(2-isoquinolin-3-yl-1h-benzoimidazole-4-carbonyl)-amino]-propionic acid methyl ester수율 50%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

145 mg (0.5 mmol) of 2-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid (synthesized in Example 1, Step 3)) was reacted with 280 mg (0.75 mmol) of HBTU and 2-amino-3-(3,5-difluoro-phenyl)-propionic acid methyl ester HCl salt (126 mg, 0.5 mmol) as described in general procedure A. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (30 mL). The organic phase was washed with 1% NaOH aq. solution, then dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography (DCM/EtOAc=1:1 then DCM/EtOAc/MeOH=15:15:1) to give 3-(3,5-difluoro-phenyl)-2-[(2-isoquinolin-3-yl-1H-benzoimidazole-4-carbonyl)-amino]-propionic acid methyl ester (120 mg, 50%). LCMS: 487 (M+1)+.

후처리

  1. washThe organic phase was washed with 1% NaOH aq. solution
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by flash column chromatography (DCM/EtOAc=1:1

출처 및 근거

ORD 기록
ord-861dd41bce3248d38985dddda92ef247
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598353B2

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