Sodium Carbonate → HCID 60197473、化合物

HRID 1631794ノート

反応式

HRID 1631794 の反応式
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([NH:15][CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:14])[CH2:7][C@@H:6]3[CH2:23][O:24][CH2:25][CH2:26][N:5]3[C:4]=2[N:3]=1.[OH:27][CH2:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=O>[OH:27][CH2:28][C:29]1[CH:34]=[C:33]([C:2]2[N:11]=[CH:10][C:9]3[N:8]([CH2:12][C:13]([NH:15][CH2:16][CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[O:14])[CH2:7][C@@H:6]4[CH2:23][O:24][CH2:25][CH2:26][N:5]4[C:4]=3[N:3]=2)[CH:32]=[CH:31][CH:30]=1

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 86670145HCID 86670145、化合物

生成物 1

HCID 60197473HCID 60197473、化合物収率 79.4%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A mixture of (R)-2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide (PREPARATION x26, 50 mg, 0.131 mmol), 3-(hydroxymethyl)phenylboronic acid (29.8 mg, 0.196 mmol), tetrakis(triphenylphospine)palladium(0) (15.13 mg, 0.013 mmol) and sodium carbonate (27.8 mg, 0.262 mmol) in 1,4-dioxane (0.5 mL) and H2O (0.25 mL) was heated to 120° C. in a microwave for 1 hour. After cooling to room temperature, the reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (amine-functionalized silica, 0-10% MeOH gradient in CHCl3) to afford the title compound as an off-white solid (47.2 mg, 0.104 mmol, 79%). 1H NMR (400 MHz, DMSO-d6) δ 1.06-1.24 (m, 2H), 1.47-1.71 (m, 3H), 2.92-3.03 (m, 3H), 3.12-3.37 (m, 5H), 3.50-3.67 (m, 2H), 3.73-3.93 (m, 4H), 3.98-4.07 (m, 2H), 4.50-4.60 (m, 3H), 5.21 (t, J=5.81 Hz, 1H), 7.26-7.38 (m, 2H), 7.50 (s, 1H), 8.06-8.11 (m, 2H), 8.18 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C24H31N5O4, 453.24. found 454.4.

後処理

  1. temperatureAfter cooling to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (amine-functionalized silica, 0-10% MeOH gradient in CHCl3)

出典と根拠

ORDレコード
ord-70dca957c83a4fc79410ea0d2bc3206f
出典データセット
uspto-grants-2014_07
特許番号
US08791107B2

反応ノート

読み込み中…