Sodium Carbonate → HCID 68195143, 화합물

HRID 2169652노트

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HRID 2169652 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:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=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>[OH:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([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:31][CH:30]=1

참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 86670145HCID 86670145, 화합물

생성물 1

HCID 68195143HCID 68195143, 화합물수율 32%

시약·촉매·용매 4

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

반응 조건

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), 4-(hydroxymethyl)phenylboronic acid (29.8 mg, 0.196 mmol), tetrakis(triphenylphosphine)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 water (0.25 mL) was heated to 120° C. for 1 hour in a microwave. 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 (silica-NH, gradient 0-10% MeOH/CHCl3) to afford a white solid, which was recrystallized from EtOH/EtOAc to give the title compound as an off-white solid (19.0 mg, 32.0%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.21 (m, 2 H), 1.48-1.71 (m, 3 H), 2.91-3.02 (m, 3 H), 3.12-3.32 (m, 5 H), 3.50-3.67 (m, 2 H), 3.73-4.08 (m, 6 H), 4.49-4.61 (m, 3 H), 5.19 (t, J=5.68 Hz, 1 H), 7.34 (d, J=8.59 Hz, 2 H), 7.47-7.51 (m, 1 H), 8.08 (t, J=5.94 Hz, 1 H), 8.16 (d, J=8.34 Hz, 2 H); ESI-MS m/z [M+H]+ calc'd for C24H31N5O4, 454.24; 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 (silica-NH, gradient 0-10% MeOH/CHCl3)
  7. customto afford a white solid, which
  8. customwas recrystallized from EtOH/EtOAc

출처 및 근거

ORD 기록
ord-b30ce3b7e13041c7a332c7cc0b0947cf
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045496B2

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