Piperidine → HCID 178423316, Verbindung

HRID 635708

Reaktionsgleichung

Reaktionsgleichung von HRID 635708
FC1C=CC(F)=C[C:3]=1[C:9]([N:11]1CCCC1)=[CH2:10].[F:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[C:24](=O)[CH3:25].N1CC[CH2:29][CH2:28]1.[CH3:32][C:33]1[N:38]=[C:37](Cl)[C:36]([N+:40]([O-])=O)=[C:35](Cl)[N:34]=1.C(N(CC)C(C)C)(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[F:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[CH:24]1[NH:11][CH:9]([CH3:10])[CH2:3][CH:32]([C:33]2[NH:38][C:37]3=[CH:28][CH:29]=[N:40][C:36]3=[CH:35][N:34]=2)[CH2:25]1

Komponenten

11

Edukt 7

HCID 8082PiperidineHCID 24479Stannous ChlorideHCID 31268PyrrolidineHCID 747941-(2,5-Difluorophenyl)ethan-1-oneHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 18511321HCID 18511321, Verbindung

Produkt 1

HCID 178423316HCID 178423316, VerbindungAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24193Titanium TetrachlorideKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

Using the method described in Example 30 by employing [1-(2,5-difluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 2′,5′-difluoro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.45 g, 6.94 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.00 g, 4.83 mmol), N,N-diisopropylethylamine (1.2 mL, 6.94 mmol), piperidine (1.1 mL, 11.1 mmol), NEt3 (1.2 mL) and SnCl2 (21 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 417 mg (26%) of 6-(2,5-difluorophenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a tan colored foam. This material (415 mg, 1.25 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.30 mL, 1.30 mmol). The solution was left to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 337 mg (19%) of the title compound as white colored needles. Mp: 279-281° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.06 (s, 4), 6.85 (s, 1), 7.42-7.55 (m, 2), 7.86-7.91 (m, 1), 12.13 (s, 1), 14.41 (s, 1). MS m/z: 329 (M+1 for free base). Anal. Calcd for C18H18F2N4.HCl.1.0H2O: C, 56.54; H, 5.50; N, 14.65. Found: C, 56.29; H, 5.61; N, 14.53.

Aufarbeitung

  1. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Quellen und Nachweise

ORD-Eintrag
ord-802342362f774f0a9f8e61e312160eef
Quelldatensatz
uspto-grants-2001_02
Patentnummer
US06187777B1

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