Hydrochloric Acid → HCID 89815492, compound

HRID 715146Notes

Reaction equation

HRID 715146 reaction equation
[ClH:1].[F:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([C:10]2[C:11]([CH3:22])=[N:12][C:13]3[C:18]([CH:19]=2)=[CH:17][N:16]=[C:15]([NH:20][CH3:21])[CH:14]=3)=[CH:5][C:4]=1[NH:23][C:24]([NH:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:25]>CC#N>[ClH:1].[F:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([C:10]2[C:11]([CH3:22])=[N:12][C:13]3[C:18]([CH:19]=2)=[CH:17][N:16]=[C:15]([NH:20][CH3:21])[CH:14]=3)=[CH:5][C:4]=1[NH:23][C:24]([NH:26][CH2:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:25]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 89815493HCID 89815493, compound

Product 1

HCID 89815492HCID 89815492, compoundYield 92.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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. customsonicate for 5 min
  2. customfreeze, lyophilize and dry

Sources & evidence

ORD record
ord-d26606c1900240978f70001fa23b73cd
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

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