Trifluoroacetic acid → HCID 71585077, compound

HRID 1430508Notes

Reaction equation

HRID 1430508 reaction equation
COC1C=CC(C[NH:8][C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([C:22]4[C:23]([Br: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)(C(F)(F)F)=O>>[NH2:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[C:14]([C:22]3[C:23]([Br:39])=[CH:24][C:25]([F:38])=[C:26]([NH:28][C:29]([NH:31][C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[O:30])[CH:27]=3)[C:15](=[O:21])[N:16]2[CH2:19][CH3:20])=[CH:11][N:10]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86713657HCID 86713657, compound

Product 1

HCID 71585077HCID 71585077, compoundYield 44%

Procedure

1-(5-(7-(4-methoxybenzylamino)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-bromo-2-fluorophenyl)-3-phenylurea (0.256 g, 0.415 mmol) was dissolved in TFA (4 mL, 51.9 mmol) and stirred at RT. After 4 h the reaction mixture was concentrated to dryness, the residue was diluted with MeOH, and the precipitated solids were removed by filtration. The filtrate was treated with satd. NaHCO3 and the resulting solid collected by filtration, rinsed with H2O, dried under vacuum, and purified by reverse phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure, the aqueous residue treated with satd. NaHCO3 and the resulting solids were collected by filtration, washed with H2O and dried to afford 1-(5-(7-amino-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-bromo-2-fluorophenyl)-3-phenylurea (90 mg, 44% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 8.68 (d, 1H, J=2.4 Hz), 8.36 (s, 1H), 8.17 (d, 1H, J=8.8 Hz), 7.70 (s, 1H), 7.65 (d, 1H, J=10.8 Hz), 7.42-7.40 (m, 2H), 7.28-7.24 (m, 2H), 6.98-6.95 (m, 1H), 6.54 (br s, 2H), 6.34 (s, 1H), 4.08 (q, 2H, J=7.2 Hz), 1.20 (t, 3H, J=7.2 Hz); MS (ESI) m/z: 496.1 (M+H+), 498.1 (M+2+H+).

Workup

  1. concentrationAfter 4 h the reaction mixture was concentrated to dryness
  2. additionthe residue was diluted with MeOH
  3. customthe precipitated solids were removed by filtration
  4. additionThe filtrate was treated with satd
  5. filtrationNaHCO3 and the resulting solid collected by filtration
  6. washrinsed with H2O
  7. customdried under vacuum
  8. custompurified by reverse phase chromatography (MeCN/H2O with 0.1% TFA)
  9. customThe organics were removed under reduced pressure
  10. additionthe aqueous residue treated with satd
  11. filtrationNaHCO3 and the resulting solids were collected by filtration
  12. washwashed with H2O
  13. customdried

Sources & evidence

ORD record
ord-caf016eaea094e02b4e67e7ede6addec
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

Loading…