Pyridine → isoquinoline-3-carboxylic acid [4-(5-benzoyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amide

HRID 1844987Notes

Reaction equation

HRID 1844987 reaction equation
[N:1]1[C:9]2[CH2:8][CH2:7][NH:6][CH2:5][C:4]=2[S:3][C:2]=1[NH:10][C:11]([C:13]1[C:18]2[NH:19][C:20]([NH:22][C:23]([C:25]3[N:26]=[CH:27][C:28]4[C:33]([CH:34]=3)=[CH:32][CH:31]=[CH:30][CH:29]=4)=[O:24])=[N:21][C:17]=2[CH:16]=[CH:15][CH:14]=1)=[O:12].N1C=CC=CC=1.[C:41](Cl)(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C(Cl)Cl.C(OCC)(=O)C>[C:41]([N:6]1[CH2:7][CH2:8][C:9]2[N:1]=[C:2]([NH:10][C:11]([C:13]3[C:18]4[N:19]=[C:20]([NH:22][C:23]([C:25]5[N:26]=[CH:27][C:28]6[C:33]([CH:34]=5)=[CH:32][CH:31]=[CH:30][CH:29]=6)=[O:24])[NH:21][C:17]=4[CH:16]=[CH:15][CH:14]=3)=[O:12])[S:3][C:4]=2[CH2:5]1)(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 7412Benzoyl chlorideHCID 178522488HCID 178522488, compound

Product 1

HCID 58026653isoquinoline-3-carboxylic acid [4-(5-benzoyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amideYield 47%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 30 mg (0.063 mmol) of isoquinoline-3-carboxylic acid [7-(4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amide (Example 198) in DCM (2 mL) was added pyridine (0.5 mL) and benzoyl chloride (0.05 mL). The mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (20 mL), the organic phase was washed with sat. aq. Na2CO3 solution, dried over Na2SO4, and concentrated under reduced pressure. The crude product was dissolved in DCM (0.5 mL), hexane was added (4 mL), and the resulting precipitate was filtered and dried to provide 17 mg (47%) of isoquinoline-3-carboxylic acid [4-(5-benzoyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amide. LCMS: 574 (M+1)+.

Workup

  1. washthe organic phase was washed with sat. aq. Na2CO3 solution
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe crude product was dissolved in DCM (0.5 mL)
  5. additionhexane was added (4 mL)
  6. filtrationthe resulting precipitate was filtered
  7. customdried

Sources & evidence

ORD record
ord-1b157c95bd4c48b0a811b4153125e777
Source dataset
uspto-grants-2015_02
Patent number
US08946259B2

Reaction notes

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