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Potassium Carbonate → (R)-6-(1-benzhydryl-3-methyl-azetidin-3-ylamino)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

HRID 519133
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HRID 519133 반응식
[NH2:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[O:12][CH2:11][C:10]1[N:5]2[C@H:6]([CH3:17])[C:7](=[O:16])[NH:8][N:9]=1.[CH:18]([N:31]1[CH2:34][C:33](OS(C)(=O)=O)([CH3:35])[CH2:32]1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>CC(O)C>[CH:18]([N:31]1[CH2:34][C:33]([NH:1][C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][CH:15]=2)[O:12][CH2:11][C:10]2[N:5]3[C@H:6]([CH3:17])[C:7](=[O:16])[NH:8][N:9]=2)([CH3:35])[CH2:32]1)([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
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참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 100652951-Benzhydryl-3-methylazetidin-3-yl methanesulfonateHCID 86727520(R)-6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

생성물 1

HCID 86727521(R)-6-(1-benzhydryl-3-methyl-azetidin-3-ylamino)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one수율 38.5%

시약·촉매·용매 1

HCID 3776
Isopropanol
용매

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온도
90 °C

실험 절차

A mixture of (R)-6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (50 g, 172 mmol), methansulfonic acid 1-benzhydryl-3-methylazetidin-3-yl ester (Preparation #14, Step B, 95 g, 258 mmol) and K2CO3 (47.6 g, 344 mmol) in iPrOH (1 L) was stirred at 90° C. for 16 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was dissolved in water (1 L) and extracted with EtOAc (3×500 mL). The combined organic phase was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (eluting with 30-60% EtOAc in petroleum ether) to give (R)-6-(1-benzhydryl-3-methyl-azetidin-3-ylamino)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (31 g, 38%) as a yellow solid. 1H NMR (CDCl3, 400 MHz): δ 8.47 (s, 1H), 7.45-7.40 (m, 4H), 7.30-7.26 (m, 4H), 7.22-7.16 (m, 2H), 6.78 (d, J=9.0 Hz, 1H), 6.08-6.02 (m, 2H), 4.64-4.57 (t, J=6.8 Hz, 1H), 4.53-4.41 (d, J=14.8 Hz, 3H), 3.30 (m, 2H), 3.15 (m, 2H), 1.65 (s, 3H), 1.46 (d, J=6.8 Hz, 3H). SFC (Table 1, Method 1) Rt=4.36 min.

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in water (1 L)
  4. extractionextracted with EtOAc (3×500 mL)
  5. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customthe residue was purified by column chromatography on silica gel (eluting with 30-60% EtOAc in petroleum ether)

출처 및 근거

ORD 기록
ord-58977cb711ca49b78e3e99e607219391
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09115151B2

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