Hydrochloric Acid → 6-[(1,1-Dioxido-4-thiomorpholinyl)methyl]-N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide

HRID 520658Notes

Reaction equation

HRID 520658 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:29]=[CH:28][CH:27]=[C:26]4[C:22]=3[CH:23]=[CH:24][NH:25]4)[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][S:42](=[O:46])(=[O:45])[CH2:41][CH2:40]1.[I-].[Na+].CCN(C(C)C)C(C)C.Cl>CC#N>[O:45]=[S:42]1(=[O:46])[CH2:43][CH2:44][N:39]([CH2:2][C:3]2[N:8]=[C:7]([C:9]([NH:11][C:12]3[CH:20]=[C:19]([C:21]4[CH:29]=[CH:28][CH:27]=[C:26]5[C:22]=4[CH:23]=[CH:24][NH:25]5)[CH:18]=[C:17]4[C:13]=3[CH:14]=[N:15][NH:16]4)=[O:10])[CH:6]=[CH:5][CH:4]=2)[CH2:40][CH2:41]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 6484228Thiomorpholine 1,1-dioxideHCID 582679866-(Chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide

Product 1

HCID 532335406-[(1,1-Dioxido-4-thiomorpholinyl)methyl]-N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

6-(Chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide (75 mg), thiomorpholine 1,1-dioxide (25 mg) and sodium iodide (25 mg) were added to a small round-bottomed flask followed by MeCN (2 ml) and DIPEA (0.048 ml). The reaction mixture was heated at 70° C. for 18 h. The reaction was cooled to RT and the solvent was removed under a stream of nitrogen. The residue was suspended in IPA (2 ml) and 2M NaOH (aq) (1 ml) was added. The mixture was stirred at RT for 2 h, heated to 50° C. for 1 h, then cooled to RT to remain stirring overnight. The reaction was heated to 60° C. for 1 h. Then 2M NaOH (aq) (0.5 ml) was added and reaction was stirred at 60° C. for 2 h. The reaction was neutralised with 2M HCl (aq.) and the solvent was removed in vacuo. The residue was dissolved in DMSO (3 ml), filtered and purified by MDAP (method K). The product-containing fractions were evaporated under a stream of nitrogen and the residues were taken up in methanol, combined and blown down to give title compound, 24 mg.

Workup

  1. temperatureThe reaction was cooled to RT
  2. customthe solvent was removed under a stream of nitrogen
  3. addition2M NaOH (aq) (1 ml) was added
  4. temperatureheated to 50° C. for 1 h
  5. temperaturecooled to RT
  6. stirringto remain stirring overnight
  7. temperatureThe reaction was heated to 60° C. for 1 h
  8. additionThen 2M NaOH (aq) (0.5 ml) was added
  9. customreaction
  10. stirringwas stirred at 60° C. for 2 h
  11. customthe solvent was removed in vacuo
  12. dissolutionThe residue was dissolved in DMSO (3 ml)
  13. filtrationfiltered
  14. custompurified by MDAP (method K)
  15. customThe product-containing fractions were evaporated under a stream of nitrogen

Sources & evidence

ORD record
ord-be73252da59248b0a16cf7293e12b56a
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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