Trifluoroacetic acid → HCID 73442528, compound

HRID 1430517Notes

Reaction equation

HRID 1430517 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]=[C:34]([F:39])[CH:33]=4)=[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:34]1[CH:33]=[C:32]([NH:31][C:29]([NH:28][C:26]2[CH:27]=[C:22]([C:14]3[C:15](=[O:21])[N:16]([CH2:19][CH3:20])[CH:17]4[CH:12]([CH:13]=3)[CH:11]=[N:10][C:9]([NH:8][CH3:7])=[CH:18]4)[C:23]([F:41])=[CH:24][C:25]=2[F:40])=[O:30])[CH:37]=[C:36]([F:38])[CH:35]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86713661HCID 86713661, compound

Product 1

HCID 73442528HCID 73442528, compoundYield 64%

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-(3,5-difluorophenyl)urea (0.112 g, 0.185 mmol) and anisole (0.202 mL, 1.849 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-(3,5-difluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea (57 mg, 64% yield). The material was dissolved in MeCN (2 mL), treated with 0.1N HCl (1.17 mL, 0.117 mmol), diluted with water (3 mL), frozen, lyophilized, triturated with Et2O and the resulting solid was collected via filtration and dried to yield 1-(3,5-difluorophenyl)-3-(5-(1-ethyl-7-(methylamino)-2-oxo-1,2,4a,8a-tetrahydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea hydrochloride (57 mg, 96% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.95 (s, 1H), 8.80 (s, 1H), 8.51 (s, 1H), 8.07 (t, 1H), 7.92 (s, 1H), 7.70 (br s, 1H), 7.40 (t, 1H), 7.15 (d, 2H), 6.82-6.77 (m, 1H), 6.43 (s, 1H), 4.15 (q, 2H), 2.91 (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-af3a0c1ec54d4792b687b4dc6473d4b4
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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