Trifluoroacetic acid → 1-(4-Chloro-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(2,5-difluorophenyl)urea

HRID 1257236Notes

Reaction equation

HRID 1257236 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[C:9](=[O:31])[N:10]([CH2:29][CH3:30])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([N:18](CC2C=CC(OC)=CC=2)[CH3:19])[CH:12]=3)=[CH:6][C:5]([NH:32][C:33]([NH:35][C:36]2[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=2[F:43])=[O:34])=[C:4]([F:44])[CH:3]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>>[Cl:1][C:2]1[C:7]([C:8]2[C:9](=[O:31])[N:10]([CH2:29][CH3:30])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH3:19])[CH:12]=3)=[CH:6][C:5]([NH:32][C:33]([NH:35][C:36]2[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=2[F:43])=[O:34])=[C:4]([F:44])[CH:3]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 867136661-(4-Chloro-5-(1-ethyl-7-((4-methoxybenzyl)(methyl)amino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(2,5-difluorophenyl)urea

Product 1

HCID 715851351-(4-Chloro-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(2,5-difluorophenyl)ureaYield 92%

Procedure

A mixture of 1-(4-chloro-5-(1-ethyl-7-((4-methoxybenzyl)(methyl)amino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(2,5-difluorophenyl)urea (314 mg, 0.505 mmol) and anisole (273 mg, 2.52 mmol) was treated with TFA (3.0 mL, 51.9 mmol) and stirred at RT for 2.5 h. The mixture was concentrated to near-dryness, treated with EtOAc and satd. NaHCO3 and the resulting solid collected via filtration and dried to afford 1-(4-chloro-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(2,5-difluorophenyl)urea (233 mg, 92% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.24 (m, 2H), 8.40 (s, 1H), 8.17 (d, J=8.7 Hz, 1H), 7.97 (m, 1H), 7.73 (s, 1H), 7.54 (d, J=11.0 Hz, 1H), 7.27 (m, 1H), 7.02 (m, 1H), 6.80 (m, 1H), 6.23 (s, 1H), 4.12 (q, J=7.1 Hz, 2H), 2.85 (d, J=4.9 Hz, 3H), 1.19 (t, J=7.0 Hz, 3H); MS (ESI) m/z: 502.2 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated to near-dryness
  2. additiontreated with EtOAc and satd
  3. filtrationNaHCO3 and the resulting solid collected via filtration
  4. customdried

Sources & evidence

ORD record
ord-8231a5146c8e4a249e41c11b62a25282
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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