Sodium hydride → HCID 136232723、化合物

HRID 1752269ノート

反応式

HRID 1752269 の反応式
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@@H:15]3[CH2:19][CH2:18][NH:17][C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[CH3:23].Cl[CH2:25][C:26]1[NH:27][C:28](=[O:36])[C:29]2[CH2:35][O:34][CH2:33][CH2:32][C:30]=2[N:31]=1.[H-].[Na+]>C1COCC1.CCOCC>[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@H:15]3[CH2:19][CH2:18][N:17]([CH2:25][C:26]4[NH:27][C:28](=[O:36])[C:29]5[CH2:35][O:34][CH2:33][CH2:32][C:30]=5[N:31]=4)[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[CH3:23]

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 71212160HCID 71212160、化合物HCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

生成物 1

HCID 136232723HCID 136232723、化合物収率 79%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

To a solution of (R)-3-[4-(4-methoxy-3-methyl-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (0.79 mmol, 250 mg) and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (0.87 mmol, 174 mg) in THF (10 mL) was added sodium hydride (60%, 2.77 mmol, 111 mg) and heated to 70° C. for 1 hour. The reaction was allowed to cool to ambient temperature, diluted with 100 mL of ether, and the resulting solid in suspension was filtered and dried under vacuum provided the title compound as an off-white solid (300 mg). Chiral resolution of 2-3-[4-(4-methoxy-3-methyl-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (300 mg) via chiral SFC chromatography on a AS-H column (60 g/min, 21×250 mm) eluting 40% IPA/0.2% DEA/CO2 (v/v) afforded 77 mg of pure material. HRMS calculated for C26H32N4O5=480.5687. found (ESI, [M+H]+) 481.2455. 1H NMR (400 MHz, MeOD) δ ppm 1.69-1.90 (m, 4H) 2.10-2.20 (m, 1H) 2.20-2.31 (m, 4H) 2.48-2.58 (m, 1H) 2.59-2.65 (m, 2H) 2.77-2.88 (m, 1H) 2.90-3.06 (m, 1H) 3.10-3.20 (m, 1H) 3.32-3.42 (m, 3H) 3.46-3.54 (m, 2H) 3.63 (t, J=8.53 Hz, 1H) 3.88-3.94 (m, 5H) 4.39 (s, 2H) 4.47 (s, 2H) 6.99 (d, J=8.53 Hz, 1H) 7.77 (s, 1H) 7.87 (dd, J=8.53, 2.01 Hz, 1H), analytical RP-HPLC (Novapak 150×3.9 mm C18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 5 min.) retention time=2.731 min.

後処理

  1. temperatureto cool to ambient temperature
  2. filtrationthe resulting solid in suspension was filtered
  3. customdried under vacuum

出典と根拠

ORDレコード
ord-120e02fa8c7641a29e4e0a4ae49c1403
出典データセット
uspto-grants-2015_10
特許番号
US09163003B2

反応ノート

読み込み中…