Hydrochloric Acid → Formic acid N-(6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-6-{[4-(1-methylethyl)-1-piperazinyl]methyl}-2-pyridinecarboxamide

HRID 1695786Notes

Reaction equation

HRID 1695786 reaction equation
Cl[CH2:2][C:3]1[N:8]=[C:7]([C:9]([NH:11][C:12]2[CH:20]=[C:19]([C:21]3[CH:22]=[N:23][C:24]([Cl:32])=[C:25]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH:26]=3)[CH:18]=[C:17]3[C:13]=2[CH:14]=[N:15][N:16]3S(C2C=CC=CC=2)(=O)=O)=[O:10])[CH:6]=[CH:5][CH:4]=1.[NH:42]1[CH2:47][CH2:46]C[CH2:44][CH2:43]1.[OH-].[Na+].Cl.C[N:52](C=[O:55])C.[CH3:56][C:57]([CH3:59])=O.O>CC(O)C>[CH:9]([OH:10])=[O:55].[Cl:32][C:24]1[N:23]=[CH:22][C:21]([C:19]2[CH:18]=[C:17]3[C:13]([CH:14]=[N:15][NH:16]3)=[C:12]([NH:11][C:9]([C:7]3[CH:6]=[CH:5][CH:4]=[C:3]([CH2:2][N:42]4[CH2:43][CH2:44][N:52]([CH:57]([CH3:59])[CH3:56])[CH2:46][CH2:47]4)[N:8]=3)=[O:10])[CH:20]=2)=[CH:26][C:25]=1[NH:27][S:28]([CH3:31])(=[O:30])=[O:29]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8082Piperidine2×HCID 14798Sodium HydroxideHCID 582558416-(Chloromethyl)-N-[6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamideHCID 86653311DMF Acetone Water

Product 1

HCID 86653313Formic acid N-(6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-6-{[4-(1-methylethyl)-1-piperazinyl]methyl}-2-pyridinecarboxamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

6-(Chloromethyl)-N-[6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide (50 mg, 0.079 mmol) and piperidine (0.5 ml, 5.05 mmol) were placed in a vial and heated in a microwave at 90° C. for 15 min. The piperidine was blown off under a stream of nitrogen to give a yellow gum. The crude residue was suspended in IPA (2 ml) and 2M NaOH (1 ml) added. The mixture was stirred at room temperature for 2 hours. The solution was neutralised with 2M HCl (aq.) and then the solvent was blown off under a stream of nitrogen. The residue was dissolved in DMF/Acetone/Water (0.3 ml:0.3 ml:30 μl) (the insoluble salt was filtered off through a filter tube) and purified by MDAP (Method E). The solvent was evaporated under a stream of nitrogen to give a brown oil which was not completely clean, so further HPLC purification was carried out. The residue was dissolved in dioxane/water (1:1, 2 ml) and freeze dried to give the title compound as a white solid (3 mg).

Workup

  1. customto give a yellow gum
  2. filtrationwas filtered off through a filter tube) and
  3. custompurified by MDAP (Method E)
  4. customThe solvent was evaporated under a stream of nitrogen
  5. customto give a brown oil which
  6. customso further HPLC purification
  7. dissolutionThe residue was dissolved in dioxane/water (1:1, 2 ml)
  8. customfreeze dried

Sources & evidence

ORD record
ord-7e83c9b3e9c04c1c8b595f70b5e1cd8f
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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