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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
ノート
印刷プレビュー

反応式

HRID 519133 の反応式
[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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 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

生成物 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-one収率 38.5%

試薬・触媒・溶媒 1

HCID 3776
Isopropanol
溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-58977cb711ca49b78e3e99e607219391
出典データセット
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09115151B2

反応ノート

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