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 1844951ノート

反応式

HRID 1844951 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-e92fdfb39a6a442e96567a0b21929219
出典データセット
uspto-grants-2015_02
特許番号
US08946259B2

反応ノート

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