Diisopropylethylamine → N-{(1S)-1-[5-chloro-2-(1-{[(1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentyl]carbonyl}piperidin-4-yl)phenyl]ethyl}acetamide

HRID 644956Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 644956
C(N(CC)C(C)C)(C)C.Cl.[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C@@H:19]1[CH2:23][C@@H:22]([N:24]([CH3:26])[CH3:25])[CH2:21][C@H:20]1[C:27]([OH:29])=O.Cl.[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([CH:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)=[C:36]([C@@H:38]([NH:40][C:41](=[O:43])[CH3:42])[CH3:39])[CH:37]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O.O>[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([CH:44]2[CH2:45][CH2:46][N:47]([C:27]([C@@H:20]3[CH2:21][C@H:22]([N:24]([CH3:25])[CH3:26])[CH2:23][C@H:19]3[C:13]3[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:12]=3[F:11])=[O:29])[CH2:48][CH2:49]2)=[C:36]([C@@H:38]([NH:40][C:41](=[O:43])[CH3:42])[CH3:39])[CH:37]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68520135(1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentanecarboxylic acid hydrochlorideHCID 68520212N-[(1S)-1-(5-chloro-2-piperidin-4ylphenyl)ethyl]acetamide hydrochloride

Produkt 1

HCID 68516348N-{(1S)-1-[5-chloro-2-(1-{[(1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentyl]carbonyl}piperidin-4-yl)phenyl]ethyl}acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

N,N-diisopropylethylamine (82.4 μL, 0.473 mmol) was added to a stirred suspension of (1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentanecarboxylic acid hydrochloride (48.2 mg, 0.158 mmol, prepared essentially as described in EXAMPLE 44), N-[(1S)-1-(5-chloro -2-piperidin-4-ylphenyl)ethyl]acetamide hydrochloride (50 mg, 0.158 mmol), and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (72.0 mg, 0.189 mmol) in N,N-dimethylformamide (1.5 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification of the crude residue by preparative reversed phase high pressure liquid chromatography on YMC Pack Pro C18 phase (gradient elution; 0-100% acetonitrile/water as eluent, 0.1% TPA modifier) afforded the title compound as a buff white solid (m/z (ES) 532 (MH+).

Aufarbeitung

  1. customprepared essentially
  2. customat ambient temperature
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude residue by preparative reversed phase high pressure liquid chromatography on YMC Pack Pro
  8. washC18 phase (gradient elution; 0-100% acetonitrile/water as eluent, 0.1% TPA modifier)

Quellen und Nachweise

ORD-Eintrag
ord-83c795d58aff41fbb58cd303b3c053d1
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07700778B2

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