Phenethylamine → HCID 89815493, compound

HRID 715145Notes

Reaction equation

HRID 715145 reaction equation
CN1CCCC1.C=C(OC(=O)[N:12]([C:14]1[CH:23]=[C:22]2[C:17]([CH:18]=[C:19]([C:25]3[CH:30]=[C:29]([NH:31][C:32](OC(C)=C)=[O:33])[C:28]([F:38])=[CH:27][C:26]=3[CH3:39])[C:20]([CH3:24])=[N:21]2)=[CH:16][N:15]=1)[CH3:13])C.[CH2:41]([NH2:49])[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>O1CCOCC1>[F:38][C:28]1[CH:27]=[C:26]([CH3:39])[C:25]([C:19]2[C:20]([CH3:24])=[N:21][C:22]3[C:17]([CH:18]=2)=[CH:16][N:15]=[C:14]([NH:12][CH3:13])[CH:23]=3)=[CH:30][C:29]=1[NH:31][C:32]([NH:49][CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:33]

Participants

5

Reactant 3

HCID 1001PhenethylamineHCID 84541-MethylpyrrolidineHCID 89827813HCID 89827813, compound

Product 1

HCID 89815493HCID 89815493, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Add 1-methylpyrrolidine (0.075 mL, 0.717 mmol) to a solution of prop-1-en-2-yl(3-(4-fluoro-2-methyl-5-(((prop-1-en-2-yloxy)carbonyl)amino)phenyl)-2-methyl-1,6-naphthyridin-7-yl)(methyl)carbamate (0.333 g, 0.717 mmol) and phenethylamine (0.091 g, 0.753 mmol) in dioxane (6 mL) and heat at 50° C. overnight. Cool to RT, add satd. NaHCO3, extract with EtOAc (3×), dry the combined organics over MgSO4 and concentrate to dryness. Dissolve the residue in dioxane (10 mL), add NaOH (1.0M, 2 mL), stir at RT for 2 h, then heat to 50° C. overnight. Add NaOH (3M, 0.5 mL), heat the mixture at 55° C. for 24 h, then add additional NaOH (3M, 0.25 mL) and heat at 60° C. for 24 h. Cool the mixture to RT, add brine, extract with EtOAc (3×), dry the combined organics over MgSO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-phenethylurea (245 mg, 77%). MS(ESI) m/z: 444.2 (M+H+). Add 0.1N HCl (6.08 mL, 0.608 mmol) to a suspension of 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-phenethylurea (0.245 g, 0.552 mmol) in MeCN (2 mL), sonicate for 5 min, freeze, lyophilize and dry to afford the title compound (244 mg, 92%) as an orange solid. 1H NMR (400 MHz, DMSO-d6): δ 9.13 (s, 1H), 8.58 (s, 1H), 8.44 (s, 1H), 8.04 (m, 2H), 7.32-7.17 (m, 6H), 6.66 (m, 2H), 3.29 (m, 2H), 2.91 (s, 3H), 2.71 (t, J=7.1 Hz, 2H), 2.51 (s, 3H), 2.01 (s, 3H).

Workup

  1. temperatureCool to RT
  2. additionadd satd
  3. extractionNaHCO3, extract with EtOAc (3×)
  4. dry with materialdry the combined organics over MgSO4
  5. concentrationconcentrate to dryness
  6. dissolutionDissolve the residue in dioxane (10 mL)
  7. additionadd NaOH (1.0M, 2 mL)
  8. temperatureheat to 50° C. overnight
  9. temperatureAdd NaOH (3M, 0.5 mL), heat the mixture at 55° C. for 24 h
  10. additionadd additional NaOH (3M, 0.25 mL)
  11. temperatureheat at 60° C. for 24 h
  12. temperatureCool the mixture to RT
  13. additionadd brine
  14. extractionextract with EtOAc (3×)
  15. dry with materialdry the combined organics over MgSO4
  16. concentrationconcentrate to dryness
  17. custompurify via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-4ef4f4c6e92a470589fb243a0cfb3855
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

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