Diisopropylethylamine → Isoquinoline-3-carboxylic acid [5-ethoxy-4-fluoro-7-(1H-imidazol-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amide

HRID 1845089Notes

Reaction equation

HRID 1845089 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:27](O)=[O:28])[C:7]2[NH:11][C:10]([NH:12][C:13]([C:15]3[N:16]=[CH:17][C:18]4[C:23]([CH:24]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)=[O:14])=[N:9][C:8]=2[C:25]=1[F:26])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.S(O)(O)(=O)=O.[NH2:68][C:69]1[NH:70][CH:71]=[CH:72][N:73]=1>CN(C=O)C.[Cl-].[Na+].O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:27](=[O:28])[NH:68][C:69]2[NH:70][CH:71]=[CH:72][N:73]=2)[C:7]2[NH:11][C:10]([NH:12][C:13]([C:15]3[N:16]=[CH:17][C:18]4[C:23]([CH:24]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)=[O:14])=[N:9][C:8]=2[C:25]=1[F:26])[CH3:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 135136Bis(2-amino-1H-imidazole) sulphateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 669405096-ethoxy-7-fluoro-2-[(isoquinoline-3-carbonyl)-amino]-3H-benzoimidazole-4-carboxylic acid

Product 1

HCID 58724447Isoquinoline-3-carboxylic acid [5-ethoxy-4-fluoro-7-(1H-imidazol-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amideYield 46.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

60 mg (0.15 mmol) of 6-ethoxy-7-fluoro-2-[(isoquinoline-3-carbonyl)-amino]-3H-benzoimidazole-4-carboxylic acid (from Example 485) and 100 mg (0.25 mmol) of HBTU were dissolved in 1.0 mL of DMF and 0.2 mL of DIEA and treated with 50 mg (0.5 mmol) of 2-aminoimidazole sulfate as described in general procedure A. Upon completion, the reaction was diluted with brine. The resulting solid was filtered, washed with water and EtOAc, and dried under vacuum to produce 32 mg (46%) of Isoquinoline-3-carboxylic acid [5-ethoxy-4-fluoro-7-(1H-imidazol-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amide. LCMS: 460 (M+1)+.

Workup

  1. filtrationThe resulting solid was filtered
  2. washwashed with water and EtOAc
  3. customdried under vacuum

Sources & evidence

ORD record
ord-a9b4fe60209b4375b8dfd3a18998b4da
Source dataset
uspto-grants-2015_02
Patent number
US08946259B2

Reaction notes

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