Sodium hydride → 2-[4-(4-Methoxy-benzoyl)-2'-oxo-[1,3']bipiperidinyl-1'-ylmethyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one

HRID 1752271ノート

反応式

HRID 1752271 の反応式
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:25]=[CH:24][C:8]([C:9]([CH:11]2[CH2:16][CH2:15][N:14]([CH:17]3[CH2:22][CH2:21][CH2:20][NH:19][C:18]3=[O:23])[CH2:13][CH2:12]2)=[O:10])=[CH:7][CH:6]=1.Cl[CH2:27][C:28]1[NH:29][C:30](=[O:38])[C:31]2[CH2:37][O:36][CH2:35][CH2:34][C:32]=2[N:33]=1>C1COCC1>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C:9]([CH:11]2[CH2:16][CH2:15][N:14]([CH:17]3[CH2:22][CH2:21][CH2:20][N:19]([CH2:27][C:28]4[NH:29][C:30](=[O:38])[C:31]5[CH2:37][O:36][CH2:35][CH2:34][C:32]=5[N:33]=4)[C:18]3=[O:23])[CH2:13][CH2:12]2)=[O:10])=[CH:24][CH:25]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 712122074-(4-Methoxybenzoyl)[1,3'-bipiperidin]-2'-oneHCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

生成物 1

HCID 1362327282-[4-(4-Methoxy-benzoyl)-2'-oxo-[1,3']bipiperidinyl-1'-ylmethyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one収率 31.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

To a stirred solution of NaH (23.8 mg, 0.942 mmol, 2.1 eq) in THF (10 mL) were added 4-(4-methoxy-benzoyl)-[1,3′]bipiperidinyl-2′-one (142 mg, 0.449 mmol, 1.0 eq) and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (90 mg, 0.449 mmol, 1.0 eq). The reaction was let to stir at 70° C. for 3 h. The solid precipitate was filtered off and washed with CH2Cl2. The solvent of the mother liquor was evaporated and the residue purified by flash chromatography on silica gel (0-15% MeOH/CH2Cl2) to afford the title compound as an off-white powder (60 mg, 0.139 mmol, 31.1% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.34 (br s, 1H) 7.94 (d, J=8.59 Hz, 2H) 7.03 (d, J=8.59 Hz, 2H) 4.14-4.54 (m, 5H) 4.06-4.10 (m, 1H) 3.45 (br s, 1H) 3.18 (d, J=5.05 Hz, 3H) 3.03 (br s, 1H) 2.85 (br s, 2H) 2.30-2.65 (m, 5H) 1.30-2.05 (m, 9H). HR-MS (m/z, MH+): 481.2461, 482.2471. HPLC retention time: 2.78 min (Agilent column 3.0×100 mm 3 um C18 column; flow rate of 1.0 mL/min with gradient from 5% to 95% acetonitrile in 10 min, 0.1% FA)

後処理

  1. filtrationThe solid precipitate was filtered off
  2. washwashed with CH2Cl2
  3. customThe solvent of the mother liquor was evaporated
  4. customthe residue purified by flash chromatography on silica gel (0-15% MeOH/CH2Cl2)

出典と根拠

ORDレコード
ord-430e5fb9c091403bb30815b8ba239de9
出典データセット
uspto-grants-2015_10
特許番号
US09163003B2

反応ノート

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