Hydrochloric Acid → 2-(1-Piperidinylmethyl)-N-[6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

HRID 520657Notes

Reaction equation

HRID 520657 reaction equation
Cl[CH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([NH:10][C:11]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]4[N:26](S(C5C=CC=CC=5)(=O)=O)[CH:27]=[CH:28][C:21]=34)[CH:17]=[C:16]3[C:12]=2[CH:13]=[N:14][N:15]3S(C2C=CC=CC=2)(=O)=O)=[O:9])[N:7]=1.[NH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1.[OH-].[Na+].Cl>CC(O)C>[N:47]1([CH2:2][C:3]2[S:4][CH:5]=[C:6]([C:8]([NH:10][C:11]3[CH:19]=[C:18]([C:20]4[CH:25]=[CH:24][N:23]=[C:22]5[NH:26][CH:27]=[CH:28][C:21]=45)[CH:17]=[C:16]4[C:12]=3[CH:13]=[N:14][NH:15]4)=[O:9])[N:7]=2)[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8082PiperidineHCID 14798Sodium HydroxideHCID 583563842-(Chloromethyl)-N-{1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-indazol-4-yl}-1,3-thiazole-4-carboxamide

Product 1

HCID 532334332-(1-Piperidinylmethyl)-N-[6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

2-(Chloromethyl)-N-{1-(phenylsulfonyl)-6-[1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-indazol-4-yl}-1,3-thiazole-4-carboxamide (40 mg) and piperidine (0.5 ml) were added to a microwave vial then heated in the microwave for 15 min at 90° C. The solvent was blown off under nitrogen. IPA (3 ml) and 2M NaOH (aq) (2 ml) were added and the reaction mixture was stirred for 29 h. The reaction was heated to 50° C. for 5 min then cooled to RT for stirring overnight. The mixture was neutralised to pH 7 with 2M HCl (aq.) and the solvent was removed under a stream of nitrogen. The resultant solid was dissolved in DMSO (2 ml), filtered and purified by MDAP (method K). The fractions were combined and solvent was removed under nitrogen. The residue was dissolved in water:1,4-dioxane (1:1) then freeze-dried to give title compound, as an orange solid, 15 mg.

Workup

  1. temperatureThe reaction was heated to 50° C. for 5 min
  2. temperaturethen cooled to RT
  3. stirringfor stirring overnight
  4. customthe solvent was removed under a stream of nitrogen
  5. dissolutionThe resultant solid was dissolved in DMSO (2 ml)
  6. filtrationfiltered
  7. custompurified by MDAP (method K)
  8. customsolvent was removed under nitrogen
  9. dissolutionThe residue was dissolved in water:1,4-dioxane (1:1)
  10. customthen freeze-dried

Sources & evidence

ORD record
ord-3a05c72351404f9aadc21bb222912217
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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