Diisopropylethylamine → isoquinoline-3-carboxylic acid [5-ethoxy-4-fluoro-7-(4-methanesulfonyl-benzylcarbamoyl)-1H-benzoimidazol-2-yl]-amide

HRID 1910250Notes

Reaction equation

HRID 1910250 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.Cl.[CH3:64][S:65]([C:68]1[CH:75]=[CH:74][C:71]([CH2:72][NH2:73])=[CH:70][CH:69]=1)(=[O:67])=[O:66]>CN(C=O)C.[Cl-].[Na+].O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:27](=[O:28])[NH:73][CH2:72][C:71]2[CH:70]=[CH:69][C:68]([S:65]([CH3:64])(=[O:67])=[O:66])=[CH:75][CH:74]=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 27292694-Methylsulfonylbenzylamine hydrochlorideHCID 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 58724486isoquinoline-3-carboxylic acid [5-ethoxy-4-fluoro-7-(4-methanesulfonyl-benzylcarbamoyl)-1H-benzoimidazol-2-yl]-amideYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

30 mg (0.08 mmol) of 6-ethoxy-7-fluoro-2-[(isoquinoline-3-carbonyl)-amino]-3H-benzoimidazole-4-carboxylic acid and 100 mg (0.25 mmol) of HBTU were dissolved in 1.0 mL of DMF and 0.3 mL of DIEA and treated with 30 mg (0.14 mmol) of 4-methanesulfonyl-benzylamine hydrochloride 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 19 mg (45%) of isoquinoline-3-carboxylic acid [5-ethoxy-4-fluoro-7-(4-methanesulfonyl-benzylcarbamoyl)-1H-benzoimidazol-2-yl]-amide. LCMS: 562 (M+1)+.

Workup

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

Sources & evidence

ORD record
ord-a513fa1f7a7343d9af3c7360fbba51d0
Source dataset
uspto-grants-2013_12
Patent number
US08598353B2

Reaction notes

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