Sodium Bicarbonate → HCID 71584838, compound

HRID 1430487Notes

Reaction equation

HRID 1430487 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:40])=[CH:24][C:25]([F:39])=[C:26]([NH:28][C:29]([NH:31][C:32]5[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[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:40])=[CH:24][C:25]([F:39])=[C:26]([NH:28][C:29]([NH:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=3)=[O:30])[CH:27]=2)[C:15]1=[O:21])[CH3:20]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 86713639HCID 86713639, compound

Product 1

HCID 71584838HCID 71584838, compoundYield 50%

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-(3-fluorophenyl)urea (267 mg, 0.421 mmol) in TFA (3 mL) was stirred at RT for 40 min. The mixture was evaporated at reduced pressure, dissolved in EtOAc, washed with satd. NaHCO3, then brine, dried (Na2SO4), concentrated in vacuo, purified by reverse phase chromatography (MeCN/water with 0.1% TFA) and partially concentrated to give an aqueous solution. The aqueous solution was diluted with satd. NaHCO3 and allowed to precipitate. The white 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-(3-fluorophenyl)urea (83 mg, 50% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.50 (br s, 1H), 8.80 (br s, 1H), 8.42 (s, 1H), 8.10-8.00 (m, 1H), 7.82 (s, 1H), 7.48 (d, 1H), 7.40-7.30 (m, 2H), 7.15-7.05 (m, 2H), 6.80-6.70 (m, 1H), 5.99 (s, 1H), 4.13 (m, 2H), 2.85 (s, 3H), 1.21 (m, 3H); MS (ES-API) m/z: 468.1 [M+H]+.

Workup

  1. customThe mixture was evaporated at reduced pressure
  2. dissolutiondissolved in EtOAc
  3. washwashed with satd
  4. dry with materialNaHCO3, then brine, dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by reverse phase chromatography (MeCN/water with 0.1% TFA)
  7. concentrationpartially concentrated
  8. customto give an aqueous solution
  9. additionThe aqueous solution was diluted with satd
  10. customto precipitate
  11. filtrationThe white solid was collected by filtration
  12. washwashed with water
  13. customdried in vacuo

Sources & evidence

ORD record
ord-e7c9ad89ce3448ac950ed26b0e9336ff
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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