Hydrochloric Acid → N-(6-{6-Chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-6-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-2-pyridinecarboxamide

HRID 1695777Notes

Reaction equation

HRID 1695777 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.[CH3:42][C@H:43]1[O:48][C@@H:47]([CH3:49])[CH2:46][NH:45][CH2:44]1.CCN(C(C)C)C(C)C.[I-].[Na+].[OH-].[Na+].Cl>CC#N.CC(O)C>[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:45]4[CH2:44][C@H:43]([CH3:42])[O:48][C@H:47]([CH3:49])[CH2:46]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

9

Reactant 6

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 6415002,6-Dimethylmorpholine, cis-HCID 582558416-(Chloromethyl)-N-[6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide

Product 1

HCID 58255823N-(6-{6-Chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-6-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-2-pyridinecarboxamideYield 3%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

6-(Chloromethyl)-N-[6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide (80 mg, 0.127 mmol) was dissolved in MeCN (1 ml). (2R,6S)-2,6-Dimethylmorpholine (16.05 mg, 0.139 mmol) was added followed by DIPEA (0.033 mL, 0.190 mmol) and then sodium iodide (18.99 mg, 0.127 mmol). The mixture was heated at 70° C. for 1 h, then the solvent was removed in vacuo to give an orange oil. IPA (1 ml) was added to the crude residue followed by aqueous NaOH (2M, 1 ml) and the solution was stirred at room temperature for 1 h. The solution was neutralised with 2M aqueous HCl and concentrated in vacuo. The residue was dissolved in DMSO (2 ml) and purified by MDAP (Method E). The resulting pale yellow gum was dissolved in DCM/MeOH (1:1) and added to the top of a 500 mg silica SPE cartridge. This was eluted with cyclohexane and the solvent was removed under a stream of nitrogen to give the title compound (2.2 mg).

Workup

  1. customthe solvent was removed in vacuo
  2. customto give an orange oil
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in DMSO (2 ml)
  5. custompurified by MDAP (Method E)
  6. dissolutionThe resulting pale yellow gum was dissolved in DCM/MeOH (1:1)
  7. additionadded to the top of a 500 mg silica SPE cartridge
  8. washThis was eluted with cyclohexane
  9. customthe solvent was removed under a stream of nitrogen

Sources & evidence

ORD record
ord-6f05323afeef4ecaabc04ab7b3a9035f
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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