Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1-(1H-imidazol-2-ylcarbamoyl)-ethyl]-amide

HRID 1844952Notes

Reaction equation

HRID 1844952 reaction equation
[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.[NH2:48][CH:49]([CH2:58][C:59]1[CH:64]=[C:63]([F:65])[CH:62]=[C:61]([F:66])[CH:60]=1)[C:50]([NH:52][C:53]1[NH:54][CH:55]=[CH:56][N:57]=1)=[O:51]>>[F:65][C:63]1[CH:64]=[C:59]([CH2:58][CH:49]([NH:48][C:20]([C:19]2[C:13]3[N:12]=[C:11]([C:3]4[N:2]=[CH:1][C:10]5[C:5]([CH:4]=4)=[CH:6][CH:7]=[CH:8][CH:9]=5)[NH:15][C:14]=3[CH:16]=[CH:17][CH:18]=2)=[O:21])[C:50](=[O:51])[NH:52][C:53]2[NH:54][CH:55]=[CH:56][N:57]=2)[CH:60]=[C:61]([F:66])[CH:62]=1

Participants

4

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 669403622-Amino-3-(3,5-difluoro-phenyl)-N-(1H-imidazol-2-yl)-propionamide HCl saltHCID 669406062-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid

Product 1

HCID 669403342-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1-(1H-imidazol-2-ylcarbamoyl)-ethyl]-amideYield 22.3%

Procedure

145 mg (0.5 mmol) of 2-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid was reacted with 280 mg (0.75 mmol) of HBTU and 2-Amino-3-(3,5-difluoro-phenyl)-N-(1H-imidazol-2-yl)-propionamide HCl salt (152 mg, 0.5 mmol) as described in general procedure A. A solid precipitated from the solution and was collected by filtration, washed with H2O and EtOAc, to give 2-isoquinolin-3-yl-1H-benzoimidazole-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1-(1H-imidazol-2-ylcarbamoyl)-ethyl]-amide (60 mg, 22%). LCMS: 538 (M+1)+.

Workup

  1. customA solid precipitated from the solution
  2. filtrationwas collected by filtration
  3. washwashed with H2O and EtOAc

Sources & evidence

ORD record
ord-5adde98ef4584467b53f467e37fd8a0c
Source dataset
uspto-grants-2015_02
Patent number
US08946259B2

Reaction notes

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