Sodium Carbonate → HCID 60197473, 화합물

HRID 2169635노트

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HRID 2169635 반응식
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

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 86670145HCID 86670145, 화합물

생성물 1

HCID 60197473HCID 60197473, 화합물수율 79.4%

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

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, 2 H), 1.47-1.71 (m, 3 H), 2.92-3.03 (m, 3 H), 3.12-3.37 (m, 5 H), 3.50-3.67 (m, 2 H), 3.73-3.93 (m, 4 H), 3.98-4.07 (m, 2 H), 4.50-4.60 (m, 3 H), 5.21 (t, J=5.81 Hz, 1 H), 7.26-7.38 (m, 2 H), 7.50 (s, 1 H), 8.06-8.11 (m, 2 H), 8.18 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C24H31N5O4, 453.24; found 454.4.

후처리

  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)

출처 및 근거

ORD 기록
ord-814f91e8227041ef9fdaf2261e579496
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045496B2

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