Methanol → HCID 20626979, compound

HRID 270723Notes

Reaction equation

HRID 270723 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[C:20](=[O:21])[N:19]([CH3:22])[C:10]3[N:11]=[C:12](S(C)(=O)=O)[N:13]=[CH:14][C:9]=3[CH:8]=2)=[CH:4][CH:3]=1.[F:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1.CO>CN1CCCC1=O>[F:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[C:20](=[O:21])[N:19]([CH3:22])[C:10]3[N:11]=[C:12]([NH:30][C:29]4[CH:31]=[CH:32][C:26]([F:25])=[CH:27][CH:28]=4)[N:13]=[CH:14][C:9]=3[CH:8]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 97314-FluoroanilineHCID 52937846HCID 52937846, compound

Product 1

HCID 20626979HCID 20626979, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-(4-fluorophenoxy)-8-methyl-2-(methylsulfonyl)pyrido[2,3-d]pyrimidin-7(8H)-one (see Example 8 replacing methyl 2-fluorophenoxyacetate with methyl 4-fluorophenoxyacetate-Step A-B, 0.35 g, 1 mmol) and 4-fluoroaniline (0.284 mL, 3 mmol) in 0.5 mL 1-methyl-2-pyrrolidinone was stirred at 110° C. for 12 hours and then cooled to room temperature. Methanol (2 mL) was added and the suspension was stirred for 30 minutes. Filtration and washing of the precipitate thoroughly with methanol followed by drying provided the crude product which was purified by column chromatography (SiO2, CH2Cl2/MeOH—95/5). The column fractions were combined and concentrated under reduced pressure to provide the free amine. This was suspended in ethyl acetate (1-2 mL) and hydrochloric acid in ether (1M, 1.2 eq) was added. Isolation of the solid via filtration and drying provided 0.101 g of the hydrochloride salt (Mass spec. M+1=381, MP=242.3-242.6° C.).

Workup

  1. temperaturecooled to room temperature
  2. stirringthe suspension was stirred for 30 minutes
  3. filtrationFiltration
  4. washwashing of the precipitate thoroughly with methanol
  5. customby drying
  6. customprovided the crude product which
  7. customwas purified by column chromatography (SiO2, CH2Cl2/MeOH—95/5)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1f78d736a2a045608836c7e6317bdd86
Source dataset
uspto-grants-2008_11
Patent number
US07449581B2

Reaction notes

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