Sodium Bicarbonate → HCID 71584839, compound

HRID 1430489Notes

Reaction equation

HRID 1430489 reaction equation
COC1C=CC([CH2:7][N:8](C)[C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([C:22]4[C:23]([F:39])=[CH:24][C:25]([F:38])=[C:26]([NH:28][C:29]([NH:31][C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)=[O:30])[CH:27]=4)[C:15](=[O:21])[N:16]3[CH2:19][CH3:20])=[CH:11][N:10]=2)=CC=1.C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O>[CH2:19]([N:16]1[C:17]2[C:12](=[CH:11][N:10]=[C:9]([NH:8][CH3:7])[CH:18]=2)[CH:13]=[C:14]([C:22]2[C:23]([F:39])=[CH:24][C:25]([F:38])=[C:26]([NH:28][C:29]([NH:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:30])[CH:27]=2)[C:15]1=[O:21])[CH3:20]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 86713640HCID 86713640, compound

Product 1

HCID 71584839HCID 71584839, compoundYield 50.4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 1-(5-(7-((4-methoxybenzyl)(methyl)amino)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)-3-phenylurea (219 mg, 0.384 mmol) in TFA (2.0 mL) was stirred at RT for 1 h. The mixture was concentrated in vacuo, dissolved in EtOAc, washed with satd. NaHCO3 and brine, dried (Na2SO4), warmed to reflux in MeOH (5 mL) with the drying agent, filtered free of drying agent (while hot), concentrated in vacuo and treated with 4M HCl/dioxane (0.2 mL). The mixture was evaporated at reduced pressure and then triturated with Et2O. The solid was collected by filtration, purified by reverse phase chromatography (MeCN/water with 0.1% TFA) and concentrated in vacuo to give an aqueous residue. The aqueous solution was treated with satd. NaHCO3 and allowed to precipitate. The solid was collected by filtration, washed with water and dried in vacuo to give 1-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)-3-phenylurea (87 mg, 50% yield). 1H NMR (400 MHz, DMSO-d6), δ 9.01 (s, 1H), 8.52 (s, 1H), 8.42 (s, 1H), 8.12 (m, 1H), 7.81 (s, 1H), 7.42-7.24 (m, 5H), 7.05-6.94 (m, 2H), 6.23 (s, 1H), 4.13 (m, 2H), 2.85 (s, 3H), 1.20 (m, 3H); MS (ES-API) m/z: 450.1 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutiondissolved in EtOAc
  3. washwashed with satd
  4. dry with materialNaHCO3 and brine, dried (Na2SO4)
  5. temperaturewarmed
  6. temperatureto reflux in MeOH (5 mL) with the drying agent
  7. filtrationfiltered free
  8. customof drying agent (while hot)
  9. concentrationconcentrated in vacuo
  10. additiontreated with 4M HCl/dioxane (0.2 mL)
  11. customThe mixture was evaporated at reduced pressure
  12. customtriturated with Et2O
  13. filtrationThe solid was collected by filtration
  14. custompurified by reverse phase chromatography (MeCN/water with 0.1% TFA)
  15. concentrationconcentrated in vacuo
  16. customto give an aqueous residue
  17. additionThe aqueous solution was treated with satd
  18. customto precipitate
  19. filtrationThe solid was collected by filtration
  20. washwashed with water
  21. customdried in vacuo

Sources & evidence

ORD record
ord-f7464d08c52f405fb868648b68794bf4
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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