Sodium Carbonate → (R)-tert-butyl 2-(2-(1H-indol-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)acetate

HRID 2169632ノート

反応式

HRID 2169632 の反応式
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C@@H:6]3[CH2:20][O:21][CH2:22][CH2:23][N:5]3[C:4]=2[N:3]=1.[NH:24]1[C:32]2[CH:31]=[CH:30][CH:29]=[C:28](B(O)O)[C:27]=2[CH:26]=[CH:25]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:24]1[C:32]2[C:27](=[C:28]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C@@H:6]5[CH2:20][O:21][CH2:22][CH2:23][N:5]5[C:4]=4[N:3]=3)[CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25]1

参加物

8

反応物 3

HCID 10340Sodium CarbonateHCID 27631731H-Indole-4-boronic acidHCID 86670103(R)-tert-butyl 2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)acetate

生成物 1

HCID 60197064(R)-tert-butyl 2-(2-(1H-indol-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)acetate収率 89.1%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒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)-tert-butyl 2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)acetate (PREPARATION x24, 100 mg, 0.293 mmol), indole-4-boronic acid (70.8 mg, 0.440 mmol), tetrakis(triphenylphosphine)palladium(0) (33.9 mg, 0.029 mmol) and sodium carbonate (62.2 mg, 0.587 mmol) in 1,4-dioxane (1 mL) and water (0.5 mL) was heated to 120° C. for 30 minutes in a microwave. After cooling to room temperature, the reaction mixture was diluted with EtOAc, filtered through Celite, washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, 20-80% EtOAc/hexane gradient) to afford the title compound as an off-white solid (110 mg, 89%). 1H NMR (400 MHz, CDCl3) δ 1.48 (s, 9 H), 3.07-3.36 (m, 3 H), 3.42-3.51 (m, 1 H), 3.62-3.79 (m, 3 H), 3.93 (dd, J=10.86, 3.28 Hz, 1 H), 4.01-4.16 (m, 2 H), 4.77 (dd, J=13.39, 2.02 Hz, 1 H), 7.22-7.31 (m, 2 H), 7.39-7.46 (m, 2 H), 7.66 (s, 1 H), 8.01 (dd, J=7.45, 0.88 Hz, 1 H), 8.26 (br s, 1H). ESI-MS m/z [M+H]+ calc'd for C23H27N5O3, 422.21; found 422.3.

後処理

  1. temperatureAfter cooling to room temperature
  2. filtrationfiltered through Celite
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2, 20-80% EtOAc/hexane gradient)

出典と根拠

ORDレコード
ord-f4000ed50fff4ac69235cf4fc4f84416
出典データセット
uspto-grants-2015_06
特許番号
US09045496B2

反応ノート

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