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

HRID 1695779Notes

Reaction equation

HRID 1695779 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][CH2:45][CH2:44][CH2:43]1.[OH-:48].[Na+].Cl>CC(O)C.CN(C=O)C.CC(C)=O.O>[CH:9]([OH:10])=[O:48].[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[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]4)[N:8]=3)=[O:10])[CH:20]=2)=[CH:26][C:25]=1[NH:27][S:28]([CH3:31])(=[O:29])=[O:30]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8082PiperidineHCID 14798Sodium HydroxideHCID 582558416-(Chloromethyl)-N-[6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide

Product 1

HCID 86653310Formic acid N-(6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-6-(1-piperidinylmethyl)-2-pyridinecarboxamide

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 86653311DMF Acetone WaterSolvent

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 amine was blown off under a stream of nitrogen to give an orange gum which was suspended in IPA (2 ml) and 2M NaOH (1 ml) was added. The mixture was stirred at room temperature for 2 hours then neutralised with 2M HCl (aq.) and 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). A further purification was carried out by HPLC and following concentration of fractions containing desired material, the residue was dissolved in dioxane/water (1:1, 2 ml) and freeze dried to afford the title compound as a white solid (3 mg).

Workup

  1. customto give an orange gum which
  2. filtrationwas filtered off through a filter tube) and
  3. custompurified by MDAP (Method E)
  4. customA further purification
  5. additioncontaining desired material
  6. dissolutionthe residue was dissolved in dioxane/water (1:1, 2 ml)
  7. customfreeze dried

Sources & evidence

ORD record
ord-f7687f87906348f288ee3622ea7511f5
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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