1-Isoquinolinamine → 3-cyclopentyl-N-isoquinolin-1-yl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionamide

HRID 1712985Notes

Reaction equation

HRID 1712985 reaction equation
Cl.[CH:2]1([CH2:7][CH:8]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)(=[O:20])=[O:19])=[CH:14][CH:13]=2)[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3]1.[C:28]1([NH2:38])[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][N:29]=1>CN(C=O)C.N1C=CC=CC=1.C(OCC)(=O)C.O.Cl.CCOCC>[CH:2]1([CH2:7][CH:8]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)(=[O:20])=[O:19])=[CH:14][CH:13]=2)[C:9]([NH:38][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=[CH:30][N:29]=2)=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

9

Reactant 2

HCID 737421-IsoquinolinamineHCID 674851743-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionic acid hydrochloride

Product 1

HCID 160425433-cyclopentyl-N-isoquinolin-1-yl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionamide

Reagents, catalysts & solvents 6

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 1049PyridineSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The title D compound, 3-cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionic acid hydrochloride (150 mg, 0.346 mmol) is slurried in DMF (3 mL) with TEA (97 μL, 0.692 mmol) and cooled to 0° C. After 45 min, isoquinolin-1-ylamine (50 mg, 0.346 mmol) in pyridine (1 mL) is added dropwise. The reaction is allowed to stir and warm to RT overnight. The reaction is diluted with ethyl acetate and water. The organic layer is separated, dried over anhydrous sodium sulfate, filtered and concentrated to afford a brown oil. Purification via flash chromatography using 0→2% methanol in ethyl acetate affords the pure product. This is dissolved in 1 M hydrochloric acid in ether and stirred at RT for 30 min, then concentrated. Dissolution in water followed by lyophilization affords 3-cyclopentyl-N-isoquinolin-1-yl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionamide, hydrochloric salt as a yellow solid: LC/MS 507.4 (M+1), 505.5 (M−1); 1H NMR (400 MHz, DMSO-D6) δ 1.2 (m, 2 H) 1.5 (m, 2 H) 1.6 (m, 2 H) 1.7 (m, 2 H) 1.8 (dd, J=13.3, 6.9 Hz, 2 H) 2.2 (dd, J=13.0, 7.5 Hz, 1 H) 2.7 (m, 5 H) 2.9 (s, 1 H) 3.1 (s, 1 H) 3.4 (d, J=11.9 Hz, 2 H) 3.8 (d, J=12.4 Hz, 2 H) 5.0 (s, 1 H) 7.8 (m, 2 H) 7.9 (m, 2 H) 8.0 (m, 2 H) 8.1 (t, J=7.6 Hz, 1 H) 8.2 (d, J=8.1 Hz, 1 H) 8.2 (d, J=6.6 Hz, 1 H) 9.0 (s, 1 H) 11.1 (s, 1 H). EC50 in primary enzyme assay 50 μM

Workup

  1. temperaturewarm to RT overnight
  2. customThe organic layer is separated
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a brown oil
  7. customPurification via flash chromatography
  8. customaffords the pure product
  9. stirringstirred at RT for 30 min
  10. concentrationconcentrated
  11. dissolutionDissolution in water

Sources & evidence

ORD record
ord-569145d97ef74d439ae327df61c02b3e
Source dataset
uspto-grants-2010_09
Patent number
US07795257B2

Reaction notes

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