Anisole → 1-(4-Chloro-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3-((4-methylpiperazin-1-yl)methyl)phenyl)urea

HRID 1257248Notes

Reaction equation

HRID 1257248 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[C:9](=[O:31])[N:10]([CH2:29][CH3:30])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([N:18](CC2C=CC(OC)=CC=2)[CH3:19])[CH:12]=3)=[CH:6][C:5]([NH:32][C:33]([NH:35][C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([CH2:42][N:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)[CH:37]=2)=[O:34])=[C:4]([F:50])[CH:3]=1.C1(OC)C=CC=CC=1>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[C:7]([C:8]2[C:9](=[O:31])[N:10]([CH2:29][CH3:30])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH3:19])[CH:12]=3)=[CH:6][C:5]([NH:32][C:33]([NH:35][C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([CH2:42][N:43]3[CH2:44][CH2:45][N:46]([CH3:49])[CH2:47][CH2:48]3)[CH:37]=2)=[O:34])=[C:4]([F:50])[CH:3]=1

Participants

4

Reactant 2

HCID 7519AnisoleHCID 86713676HCID 86713676, compound

Product 1

HCID 715847301-(4-Chloro-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3-((4-methylpiperazin-1-yl)methyl)phenyl)ureaYield 77.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A mixture of 1-(4-chloro-5-(1-ethyl-7-((4-methoxybenzyl)(methyl)amino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3-((4-methylpiperazin-1-yl)methyl)phenyl)urea (78 mg, 0.112 mmol) and anisole (60 mg, 0.559 mmol) was stirred in TFA (2 mL) at RT for 2 h. The mixture was 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 was treated with satd. NaHCO3. The mixture was extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford 1-(4-chloro-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3-((4-methylpiperazin-1-yl)methyl)phenyl)urea (50 mg, 76% yield). MS (ESI) m/z: 578.2 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-6deba962d32e4c38aa1eadeaebe6ee75
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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