Sodium Iodide → Formic acid 6-(4-morpholinylmethyl)-N-[6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide

HRID 1616054Notes

Reaction equation

HRID 1616054 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:26]=[CH:25][N:24]=[C:23]4[NH:27][CH:28]=[CH:29][C:22]=34)[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:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.CCN(C(C)C)C(C)C.[I-].[Na+].C[Si](C)(C)[O-].[K+]>CC#N.C1COCC1>[CH:9]([OH:10])=[O:42].[N:39]1([CH2:2][C:3]2[N:8]=[C:7]([C:9]([NH:11][C:12]3[CH:20]=[C:19]([C:21]4[CH:26]=[CH:25][N:24]=[C:23]5[NH:27][CH:28]=[CH:29][C:22]=45)[CH:18]=[C:17]4[C:13]=3[CH:14]=[N:15][NH:16]4)=[O:10])[CH:6]=[CH:5][CH:4]=2)[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 23668039Potassium trimethylsilanolateHCID 582679856-(Chloromethyl)-N-[1-(phenylsulfonyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide

Product 1

HCID 67158677Formic acid 6-(4-morpholinylmethyl)-N-[6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamideYield 62.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

6-(Chloromethyl)-N-[1-(phenylsulfonyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide (0.05 g, 0.09 mmol) was dissolved in MeCN (0.5 ml) and added to a vessel containing morpholine (0.1 mmol). DIPEA (0.026 ml, 0.15 mmol) and sodium iodide (0.015 g, 0.1 mmol) were then added and the mixture was heated to 70° C. for 18 hr. Potassium trimethylsilanolate (0.5 mmol, 0.063 g), dissolved in THF (0.25 ml) was then added and the mixture was heated at 50° C. for 24 hrs. After cooling the solution was quenched with aqueous MeCN (50:50, 1 ml) and neutralised. Solvent was removed in a blowdown unit. The sample was then dissolved in DMF (200 μl), Acetone (200 μl) and water (20 μl) and purified by Mass Directed AutoPrep HPLC (Method F). The solvent was removed in vacuo using the Genevac to give the title compound (14 mg).

Workup

  1. additionadded to a vessel
  2. additionwas then added
  3. temperaturethe mixture was heated at 50° C. for 24 hrs
  4. temperatureAfter cooling the solution
  5. customwas quenched with aqueous MeCN (50:50, 1 ml)
  6. customSolvent was removed in a blowdown unit
  7. dissolutionThe sample was then dissolved in DMF (200 μl)
  8. customAcetone (200 μl) and water (20 μl) and purified by Mass Directed AutoPrep HPLC (Method F)
  9. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-4dd0c5f722bf44c0853fa18c05d3cca4
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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