Hydrochloric Acid → N-(2-Methyl-3-(5-(5-(4-methylpiperazin-1-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

HRID 557538Notes

Reaction equation

HRID 557538 reaction equation
C[O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[C:10]([CH3:27])=[C:11]([NH:15][C:16]([C:18]3[S:22][C:21]4[CH2:23][CH2:24][CH2:25][CH2:26][C:20]=4[CH:19]=3)=[O:17])[CH:12]=[CH:13][CH:14]=2)=[CH:5][C:4]=1[NH:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]2[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]2)=[CH:31][N:30]=1.Cl.ClCCl.O>O1CCOCC1>[CH3:27][C:10]1[C:9]([C:6]2[CH:5]=[C:4]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([N:35]4[CH2:36][CH2:37][N:38]([CH3:41])[CH2:39][CH2:40]4)=[CH:31][N:30]=3)[C:3](=[O:2])[NH:8][CH:7]=2)=[CH:14][CH:13]=[CH:12][C:11]=1[NH:15][C:16]([C:18]1[S:22][C:21]2[CH2:23][CH2:24][CH2:25][CH2:26][C:20]=2[CH:19]=1)=[O:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 6344DichloromethaneHCID 59740597N-(3-(6-Methoxy-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-carboxamide

Product 1

HCID 59740580N-(2-Methyl-3-(5-(5-(4-methylpiperazin-1-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideYield 80%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 25 mL, round-bottomed, single-necked flask equipped with a magnetic stirring bar and a condenser was placed N-(3-(6-methoxy-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-carboxamide (18) (0.070 g, 0.13 mmol) and 3 N HCl (1 mL) in dioxane (3 mL). The reaction mixture was heated at 100° C. for 2 h. To this was added dichloromethane (10 mL) and H2O (10 mL), and the layers were separated. The aqueous phase was extracted with dichloromethane (3×5 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-33% MeOH in dichloromethane, to afford 0.053 g (80%) of N-(2-methyl-3-(5-(5-(4-methylpiperazin-1-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (19); Exact mass m/z 554.25; M=H m/z 555.20.

Workup

  1. customIn a 25 mL, round-bottomed, single-necked flask equipped with a magnetic stirring bar and a condenser
  2. customthe layers were separated
  3. extractionThe aqueous phase was extracted with dichloromethane (3×5 mL)
  4. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude mixture was purified by column chromatography, gradient 0-33% MeOH in dichloromethane

Sources & evidence

ORD record
ord-8b74d8558076403893ff4687b84a3ae9
Source dataset
uspto-grants-2011_11
Patent number
US08058446B2

Reaction notes

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