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 2169632노트

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HRID 2169632 반응식
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

참가 물질

8

반응물 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

생성물 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)acetate수율 89.1%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-f4000ed50fff4ac69235cf4fc4f84416
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045496B2

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