Hydrochloric Acid → HCID 71584756, compound

HRID 1257252Notes

Reaction equation

HRID 1257252 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])=[CH:4][C:3]=1[C:19]1[C:20](=[O:46])[N:21]([CH2:44][CH3:45])[C:22]2[C:27]([CH:28]=1)=[CH:26][N:25]=[C:24]([NH:29][C:30]([C@@H:32]1[CH2:36][CH2:35][CH2:34][N:33]1C(OC(C)(C)C)=O)=[O:31])[CH:23]=2.Cl.CO>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH:9][C:10]([NH:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:11])=[CH:4][C:3]=1[C:19]1[C:20](=[O:46])[N:21]([CH2:44][CH3:45])[C:22]2[C:27]([CH:28]=1)=[CH:26][N:25]=[C:24]([NH:29][C:30]([C@@H:32]1[CH2:36][CH2:35][CH2:34][NH:33]1)=[O:31])[CH:23]=2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 86713679HCID 86713679, compound

Product 1

HCID 71584756HCID 71584756, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (S)-tert-butyl 2-((3-(2-chloro-4-fluoro-5-(3-phenylureido)phenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)carbamoyl)pyrrolidine-1-carboxylate (115 mg, 0.177 mmol) in dioxane (3 mL) was treated with 1.25 N HCl in MeOH (2.8 mL, 3.5 mmol) and heated at 50° C. for 2 h. The mixture was concentrated to dryness, treated with satd. NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure and the aqueous residue treated with satd. NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford (S)—N-(3-(2-chloro-4-fluoro-5-(3-phenylureido)phenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)pyrrolidine-2-carboxamide (27 mg, 30% yield). MS (ESI) m/z: 549.2 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. additiontreated with satd
  3. extractionNaHCO3 and extracted with EtOAc (2×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  8. customThe organics were removed under reduced pressure
  9. additionthe aqueous residue treated with satd
  10. extractionNaHCO3 and extracted with EtOAc (2×)
  11. washThe combined organics were washed with brine
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-5de56109dd79443eaf3d435e736a208f
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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