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

HRID 2180972ノート

反応式

HRID 2180972 の反応式
[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]

参加物

6

反応物 3

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

生成物 1

HCID 155504831-Boc-4-(4-Chloroquinazolin-6-ylethynyl)piperidine収率 94.3%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-25714534ce974272957d0c4571587de8
出典データセット
uspto-grants-2005_05
特許番号
US06890924B2

反応ノート

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