Trifluoroacetic acid → 6-[(4-Fluorophenyl)oxy]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-3-pyridinecarboxamide

HRID 534800Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 534800
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]([CH3:39])[C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[C@@H:27]([CH3:38])[CH2:26]4)=[CH:20][CH:19]=3)=[O:16])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]([CH3:39])[C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][NH:28][C@@H:27]([CH3:38])[CH2:26]4)=[CH:20][CH:19]=3)=[O:16])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 592621161,1-Dimethylethyl (2S)-4-({4-[({6-[(4-fluorophenyl)oxy]-3-pyridinyl}carbonyl) (methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

Produkt 1

HCID 237290236-[(4-Fluorophenyl)oxy]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-3-pyridinecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 1,1-dimethylethyl (2S)-4-({4-[({6-[(4-fluorophenyl)oxy]-3-pyridinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D16) (32.39 g, 0.0606 mol) in DCM (150 mL) was cooled in an ice/water bath and TFA (80 mL) was added drop-wise over 10 minutes. The reaction mixture was stirred at room temperature overnight then concentrated to a yellow gum. The gum was dissolved in MeOH (100 mL) and loaded onto SCX resin (150 g, pre-washed with MeOH). Elution with MeOH (750 mL) gave unchanged TFA salt of the title compound, and elution with 2M NH3 in MeOH (750 mL) gave title compound free base. The recovered TFA salt was treated in a similar manner to that described above using further SCX resin (100 g) to give a further batch of title compound free base. The two batches of the free base were combined in DCM and concentrated to give the title compound as a pale yellow gum (26.78 g). δH (CDCl3, 400 MHz) 8.07 (1H, d), 7.65 (1H, dd), 7.22 (2H, d), 7.04 (6H, m), 6.70 (1H, d), 3.48 (3H, s), 3.42 (2H, s), 2.89 (3H, m), 2.68 (2H, d), 1.97 (1H, m), 1.64 (1H, t), 1.49 (1H bs), 1.00 (3H, d). MS (ES): MH+ 435.1.

Aufarbeitung

  1. concentrationthen concentrated to a yellow gum
  2. dissolutionThe gum was dissolved in MeOH (100 mL)
  3. washloaded onto SCX resin (150 g, pre-washed with MeOH)
  4. washElution with MeOH (750 mL)
  5. customgave unchanged
  6. washTFA salt of the title compound, and elution with 2M NH3 in MeOH (750 mL)

Quellen und Nachweise

ORD-Eintrag
ord-77c6920a8dfd4d97b11a8e912c23dae9
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08853218B2

Notizen zur Reaktion

Wird geladen…