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

HRID 1264059Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1264059
[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)piperidine

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 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

Quellen und Nachweise

ORD-Eintrag
ord-0d102bbc75eb498ab8f73cf9e7c6ea7d
Quelldatensatz
uspto-grants-2003_04
Patentnummer
US06541481B2

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