Morpholine → HCID 58255775, compound

HRID 1695778Notes

Reaction equation

HRID 1695778 reaction equation
[Cl:1][C:2]1[C:7]([N:8]([S:19]([CH3:22])(=[O:21])=[O:20])C(C2C=CC=C(CCl)N=2)=O)=[CH:6][C:5]([C:23]2[CH:31]=[C:30]3[C:26]([CH:27]=[N:28][N:29]3S(C3C=CC=CC=3)(=O)=O)=[C:25]([NH:41][C:42]([C:44]3[CH:49]=[CH:48][CH:47]=[C:46]([CH2:50]Cl)[N:45]=3)=[O:43])[CH:24]=2)=[CH:4][N:3]=1.[NH:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1>>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:23]2[CH:31]=[C:30]3[C:26]([CH:27]=[N:28][NH:29]3)=[C:25]([NH:41][C:42]([C:44]3[CH:49]=[CH:48][CH:47]=[C:46]([CH2:50][N:52]4[CH2:57][CH2:56][O:55][CH2:54][CH2:53]4)[N:45]=3)=[O:43])[CH:24]=2)=[CH:6][C:7]=1[NH:8][S:19]([CH3:22])(=[O:20])=[O:21]

Participants

3

Reactant 2

HCID 8083MorpholineHCID 86653309HCID 86653309, compound

Product 1

HCID 58255775HCID 58255775, compoundYield 24.2%

Conditions

Temperature
90 °C

Procedure

N-{2-Chloro-5-[4-({[6-(chloromethyl)-2-pyridinyl]carbonyl}amino)-1-(phenylsulfonyl)-1H-indazol-6-yl]-3-pyridinyl}-6-(chloromethyl)-N-(methylsulfonyl)-2-pyridinecarboxamide (60 mg, 0.061 mmol) and morpholine (0.5 ml, 5.74 mmol) were placed in a vial and heated in a microwave at 90° C. for 15 min. The mixture was concentrated by blow down under a stream of nitrogen. The crude residue was suspended in IPA (2 ml) and 2M NaOH (1 ml) added. The mixture was stirred at room temperature for 2 h. The solvent was removed by blow down and the residue purified by MDAP (Method E) (3×800 μl injections in DMSO, the insoluble salt was filtered off through a filter tube). Product-containing fractions were combined and the solvent removed in vacuo. The residue was dissolved in DCM:MeOH and added to the top of a 1 g silica cartridge that was subsequently eluted with 0-5% MeOH/DCM over 5 column volumes. No separation was observed, hence all fractions were combined and the solvent removed under a stream of nitrogen. The residue was dissolved in DMF/Acetone/Water (0.2 ml:0.2 ml:20 μl) and purified by MDAP (Method E). Product-containing fractions were combined and the solvent removed in vacuo. The resulting oil was triturated with ether to give the title compound as a cream solid (8 mg).

Workup

  1. concentrationThe mixture was concentrated by blow down under a stream of nitrogen
  2. addition2M NaOH (1 ml) added
  3. customThe solvent was removed by blow down
  4. customthe residue purified by MDAP (Method E) (3×800 μl injections in DMSO
  5. filtrationthe insoluble salt was filtered off through a filter tube)
  6. customthe solvent removed in vacuo
  7. dissolutionThe residue was dissolved in DCM
  8. additionMeOH and added to the top of a 1 g silica cartridge that
  9. washwas subsequently eluted with 0-5% MeOH/DCM over 5 column volumes
  10. customNo separation
  11. customthe solvent removed under a stream of nitrogen
  12. dissolutionThe residue was dissolved in DMF/Acetone/Water (0.2 ml:0.2 ml:20 μl)
  13. custompurified by MDAP (Method E)
  14. customthe solvent removed in vacuo
  15. customThe resulting oil was triturated with ether

Sources & evidence

ORD record
ord-9856a13f3bb9423a8ddb328047962044
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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