Methanol → HCID 20626925, compound

HRID 1375585Notes

Reaction equation

HRID 1375585 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:3]=1[O:4][C:5]1[C:18](=[O:19])[N:17]([CH3:20])[C:8]2[N:9]=[C:10](S(C)(=O)=O)[N:11]=[CH:12][C:7]=2[CH:6]=1.[F:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1.CO>CN1CCCC1=O>[Cl:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:3]=1[O:4][C:5]1[C:18](=[O:19])[N:17]([CH3:20])[C:8]2[N:9]=[C:10]([NH:31][C:30]3[CH:32]=[CH:33][C:27]([F:26])=[CH:28][CH:29]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 97314-FluoroanilineHCID 23434545HCID 23434545, compound

Product 1

HCID 20626925HCID 20626925, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-(2,6-dichlorophenoxy)-8-methyl-2-(methylsulfonyl)pyrido[2,3-d]pyrimidin-7(8H)-one (see Example 12—Step A–B, (replacing methyl 2-fluorophenoxyacetate with methyl 2,6-dichlorophenoxyacetate) 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 0.131 g of the hydrochloride salt (Mass spec. M+1=430, MP=248.2–249.1° 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-4e1b041fb7f94f3a93c7f751aa1174a4
Source dataset
uspto-grants-2007_01
Patent number
US07169794B2

Reaction notes

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