1,1-dimethylethyl (2S)-4-({4-[({4-[(3-fluorophenyl)amino]-1-piperidinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate → 4-[(3-Fluorophenyl)amino]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-1-piperidinecarboxamide

HRID 906379Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 906379
[F:1][C:2]1[CH:3]=[C:4]([NH:8][CH:9]2[CH2:14][CH2:13][N: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])[CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:8][CH:9]2[CH2:10][CH2:11][N: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])[CH2:13][CH2:14]2)[CH:5]=[CH:6][CH:7]=1

Komponenten

4

Edukt 1

HCID 576995151,1-dimethylethyl (2S)-4-({4-[({4-[(3-fluorophenyl)amino]-1-piperidinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

Produkt 1

HCID 236344374-[(3-Fluorophenyl)amino]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-1-piperidinecarboxamideAusbeute 80,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

A solution of 1,1-dimethylethyl (2S)-4-({4-[({4-[(3-fluorophenyl)amino]-1-piperidinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D33) (67 mg, 0.124 mmol) in DCM (2.5 ml) and TFA (0.5 ml) was stirred at room temp for ˜1.5 h. The solvent was removed in vacuo and the residue partitioned between DCM and saturated aqueous NaHCO3 solution. The aqueous layer was further extracted with DCM and the combined organic layers were dried and concentrated to give the crude product as a pale yellow oil. Column chromatography eluting with 0-10% (2M NH3 in MeOH)/DCM gave the title compound as a pale yellow oil (44 mg). δH (CDCl3, 400 MHz) 7.27 (2H, d), 7.05 (3H, m), 6.34 (1H, m), 6.29 (1H, m), 6.21 (1H, m), 3.77 (2H, d), 3.62 (1H, d), 3.47 (2H, m), 3.38 (1H, m), 3.21 (3H, s), 2.93 (3H, m), 2.75 (3H, m), 2.20 (1H+H2O, br. s), 2.05 (1H, td), 1.85 (2H, m), 1.72 (1H, m), 1.16 (2H, m), 1.04 (3H, d). MS (ES): MH+ 440.2.

Aufarbeitung

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between DCM and saturated aqueous NaHCO3 solution
  3. extractionThe aqueous layer was further extracted with DCM
  4. customthe combined organic layers were dried
  5. concentrationconcentrated
  6. customto give the crude product as a pale yellow oil
  7. washColumn chromatography eluting with 0-10% (2M NH3 in MeOH)/DCM

Quellen und Nachweise

ORD-Eintrag
ord-00d1304013ad43cb818417ebaa6b8078
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08012981B2

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