Diisopropylethylamine → MK-0493 free base

HRID 2415559Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2415559
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.[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)=[C:37]([C@@H:39]([NH:41][C:42](=[O:44])[CH3:43])[CH3:40])[CH:38]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>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:48]2[CH2:47][CH2:46][CH:45]([C:36]3[CH:35]=[CH:34][C:33]([Cl:32])=[CH:38][C:37]=3[C@@H:39]([NH:41][C:42](=[O:44])[CH3:43])[CH3:40])[CH2:50][CH2:49]2)=[O:29])[CH2:16]1)([CH3:14])([CH3:13])[CH3:12]

Komponenten

6

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 67212109(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochlorideHCID 68520212N-[(1S)-1-(5-chloro-2-piperidin-4ylphenyl)ethyl]acetamide hydrochloride

Produkt 1

HCID 11642422MK-0493 free baseAusbeute 99,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

N,N-diisopropylethylamine (5.86 mL, 33.6 mmol) was added to a stirred suspension of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochloride (3-9) (3.07 g, 9.61 mmol), N-[(1S)-1-(5-chloro-2-piperidin-4-ylphenyl)ethyl]acetamide hydrochloride (3.05 g, 9.61 mmol), and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluoro-phosphate (4.38 g, 11.5 mmol) in N,N-dimethylfoimamide (20 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured 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 residue by flash chromatography on silica gel (gradient elution; 0-9% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent) provided 3-10 (5.2 g) as a foam m/z (ES) 546 (MH+).

Aufarbeitung

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by flash chromatography on silica gel (gradient elution; 0-9% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-49eeaa2b4a614b9db44f2795ed66b821
Quelldatensatz
uspto-grants-2004_11
Patentnummer
US06818658B2

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