Anisole → HCID 71585136, compound

HRID 1257237Notes

Reaction equation

HRID 1257237 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([NH:12][C:13]2[CH:18]=[C:17]([C:19]3[C:20](=[O:42])[N:21]([CH2:40][CH3:41])[C:22]4[C:27]([CH:28]=3)=[CH:26][N:25]=[C:24]([N:29](CC3C=CC(OC)=CC=3)[CH3:30])[CH:23]=4)[C:16]([CH3:43])=[CH:15][C:14]=2[F:44])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.C1(OC)C=CC=CC=1>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([NH:12][C:13]2[CH:18]=[C:17]([C:19]3[C:20](=[O:42])[N:21]([CH2:40][CH3:41])[C:22]4[C:27]([CH:28]=3)=[CH:26][N:25]=[C:24]([NH:29][CH3:30])[CH:23]=4)[C:16]([CH3:43])=[CH:15][C:14]=2[F:44])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

4

Reactant 2

HCID 7519AnisoleHCID 86713667HCID 86713667, compound

Product 1

HCID 71585136HCID 71585136, compoundYield 73.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 1-(3-chloro-5-fluorophenyl)-3-(5-(1-ethyl-7-((4-methoxybenzyl)(methyl)amino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)urea (0.105 g, 0.170 mmol) in TFA (3 mL) was treated with anisole (0.093 ml, 0.849 mmol) and stirred at RT for 4 h. The mixture was concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The combined fractions were neutralized with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with water, then brine, dried over Na2SO4 and concentrated to dryness to afford 1-(3-chloro-5-fluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)urea (62 mg, 73% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.54 (s, 1H), 8.69 (s, 1H), 8.40 (s, 1H), 7.85 (d, J=8.4 Hz, 1H), 7.66 (s, 1H), 7.35 (s, 1H), 7.27 (dt, J=11.3, 2.1 Hz, 1H), 7.14 (d, J=12.1 Hz, 1H), 7.00-6.95 (m, 2H), 6.24 (s, 1H), 4.14 (q, J=7.1 Hz, 2H), 2.85 (d, J=4.9 Hz, 3H), 2.07 (s, 3H), 1.21 (t, J=7.0 Hz, 3H); MS (ESI) m/z: 498.2 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. custompurified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  3. extractionNaHCO3, extracted with EtOAc (2×)
  4. washthe combined organics were washed with water
  5. dry with materialbrine, dried over Na2SO4
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-75498b2ea0b4489e823c24147cf3a2c2
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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