Diisopropylethylamine → Methyl 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}-1,2,3,6-Tetrahydropyridin-4-yl)-5-Chlorophenyl]Propanoate

HRID 2415548Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2415548
C(N(CC)C(C)C)(C)C.Cl.[C:11]([N:15]1[CH2:19][C@@H:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[C@H:17]([C:28](O)=[O:29])[CH2:16]1)([CH3:14])([CH3:13])[CH3:12].[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([C:44]2[CH2:45][CH2:46][NH:47][CH2:48][CH:49]=2)=[C:36]([CH:38]([CH3:43])[C:39]([O:41][CH3:42])=[O:40])[CH:37]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.ON1C2N=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[C:11]([N:15]1[CH2:19][C@@H:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[C@H:17]([C:28]([N:47]2[CH2:46][CH:45]=[C:44]([C:35]3[CH:34]=[CH:33][C:32]([Cl:31])=[CH:37][C:36]=3[CH:38]([CH3:43])[C:39]([O:41][CH3:42])=[O:40])[CH2:49][CH2:48]2)=[O:29])[CH2:16]1)([CH3:12])([CH3:14])[CH3:13]

Komponenten

8

Edukt 6

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22640763HCID 22640763, VerbindungHCID 67212109(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochloride

Produkt 1

HCID 69362634Methyl 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}-1,2,3,6-Tetrahydropyridin-4-yl)-5-Chlorophenyl]Propanoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

N,N-diisopropylethylamine (1.00 mL, 5.76 mmol) was added to a stirred suspension of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid (1-7) (0.614 g, 1.92 mmol), methyl 2-[5-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]propanoate (2-3) (0.605 g, 1.92 mmol), O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.876 g, 2.30 mmol) and 1-hydroxy-7-azabenzotriazole (0.314 g, 2.30 mmol) in N,N-dimethylformamide (3.8 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with ethyl acetate. The combined organic extracts were washed with water, brine, dried (Na2SO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0-15% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent) provided 2-4 as a pale yellow oil; (m/z (ES) 545 (MH+).

Aufarbeitung

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 0-15% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-bbd24837e3544af2ab8fa170ae4ab20f
Quelldatensatz
uspto-grants-2004_11
Patentnummer
US06818658B2

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