Diisopropylamine → 1-Boc-4-(4-Chloroquinazolin-6-ylethynyl)piperidine

HRID 2055150Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2055150
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[CH:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:16][C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24](I)[CH:25]=2)[N:20]=[CH:19][N:18]=1.C(NC(C)C)(C)C>C1COCC1.[Cu]I>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:24]2[CH:25]=[C:26]3[C:21](=[CH:22][CH:23]=2)[N:20]=[CH:19][N:18]=[C:17]3[Cl:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 7912DiisopropylamineHCID 111738094-Chloro-6-iodoquinazolineHCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylate

Produkt 1

HCID 155504831-Boc-4-(4-Chloroquinazolin-6-ylethynyl)piperidineAusbeute 94,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of 4-ethynyl-piperidine-1-carboxylic acid tert-butyl ester (1.12 g, 5.35 mmol), 4-chloro-6-iodoquinazoline (1.35 g, 4.65 mmol), dichlorobis(triphenylphosphine) palladium(II) (0.16 g, 0.23 mmol), copper(I) iodide (0.044 g, 0.23 mmol), and diisopropylamine (0.47 g, 4.65 mmol) in anhydrous THF (20 mL) was stirred at room temperature under nitrogen for 2 hours. After concentration, the residue was dissolved in CH2Cl2 (100 mL), washed with aqueous NH4Cl and brine, dried over sodium sulfate, and concentrated to give the crude product as brown oil. Purification by silica gel column using 20% EtOAc in hexane afforded 1.63 g (94%) of the title compound as a sticky, yellow oil: 1H NMR (CDCl3) δ 1.45 (s, 9H), 1.67-1.75 (m, 2H), 1.87-1.92 (m, 2H), 2.84 (m, 1H), 3.20-3.26 (m, 2H), 3.78 (br d, 2H), 7.88 (dd, 1H), 7.97 (d, 1H), 8.26 (d, 1H), 9.00 (s, 1H).

Aufarbeitung

  1. concentrationAfter concentration
  2. dissolutionthe residue was dissolved in CH2Cl2 (100 mL)
  3. washwashed with aqueous NH4Cl and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customto give the crude product as brown oil
  7. customPurification by silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-cf08e76bbaef4e7c9bc575a86c10f1df
Quelldatensatz
uspto-grants-2008_02
Patentnummer
US07332493B2

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