Trifluoroacetic acid → HCID 73442527, compound

HRID 1430515Notes

Reaction equation

HRID 1430515 reaction equation
COC1C=CC([CH2:7][N:8](C)[C:9]2[N:10]=[CH:11][CH:12]3[CH:17]([CH:18]=2)[N:16]([CH2:19][CH3:20])[C:15](=[O:21])[C:14]([C:22]2[C:23]([F:41])=[CH:24][C:25]([F:40])=[C:26]([NH:28][C:29]([NH:31][C:32]4[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=4[F:39])=[O:30])[CH:27]=2)=[CH:13]3)=CC=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:39][C:33]1[CH:34]=[CH:35][C:36]([F:38])=[CH:37][C:32]=1[NH:31][C:29]([NH:28][C:26]1[CH:27]=[C:22]([C:14]2[C:15](=[O:21])[N:16]([CH2:19][CH3:20])[CH:17]3[CH:12]([CH:13]=2)[CH:11]=[N:10][C:9]([NH:8][CH3:7])=[CH:18]3)[C:23]([F:41])=[CH:24][C:25]=1[F:40])=[O:30]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86713660HCID 86713660, compound

Product 1

HCID 73442527HCID 73442527, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(5-(7-((4-methoxybenzyl)(methyl)amino)-1-ethyl-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)-3-(2,5-difluorophenyl)urea (0.129 g, 0.213 mmol) and anisole (0.233 mL, 2.130 mmol) in DCM (2 mL) was treated with TFA (2 mL, 26.0 mmol) and stirred at RT overnight. The mixture was concentrated to dryness, treated with EtOAc and satd. NaHCO3, stirred for 1 h and the resulting solid collected via filtration and dried to afford 1-(2,5-difluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea (84 mg, 81% yield). The material was suspended in MeCN (2 mL), treated with 0.5 N HCl (2.076 mL, 0.208 mmol), diluted with water (2 mL), frozen, lyophilized, triturated with Et2O and the resulting solid was collected via filtration and dried to yield 1-(2,5-difluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea hydrochloride (85 mg, 94% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.24 (s, 1H), 9.18 (s, 1H), 8.53 (s, 1H), 8.18 (t, 1H), 8.02-7.97 (m, 1H), 7.94 (s, 1H), 7.90 (br s, 1H), 7.42 (t, 1H), 7.32-7.26 (m, 1H), 6.84-6.80 (m, 1H), 6.48 (s, 1H), 4.19 (q, 2H), 2.94 (s, 3H), 1.21 (t, 3H); MS (ESI) m/z: 486.2 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. additiontreated with EtOAc and satd
  3. stirringNaHCO3, stirred for 1 h
  4. filtrationthe resulting solid collected via filtration
  5. customdried

Sources & evidence

ORD record
ord-a70c8e0e9ae844009694daa7b450f0ca
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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