Tetrahydrofuran → (S)-7-(quinuclidin-3-yl)-8,9-dihydro-[1,4]diazepino[6,7,1-hi]indazol-6(7H)-one

HRID 2369877ノート

反応式

HRID 2369877 の反応式
N12CCC(CC1)[C@H]([NH:9][CH2:10][CH2:11][N:12]1[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[C:21]([O-])=O)[CH:14]=[N:13]1)C2.[Li+].[CH:25]([N:28](CC)[CH:29]([CH3:31])C)(C)[CH3:26].CCCP1(OP(CCC)(=O)OP([CH2:49][CH2:50][CH3:51])(=O)O1)=O.C1C[O:55]CC1>>[N:28]12[CH2:49][CH2:50][CH:51]([CH2:31][CH2:29]1)[CH:26]([C@@H:16]1[C:17](=[O:55])[CH:18]=[C:19]3[CH:21]=[N:9][CH:10]=[CH:11][N:12]4[C:20]3=[C:15]1[CH2:14][NH:13]4)[CH2:25]2

参加物

5

反応物 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 66899683lithium (S)-1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indazole-7-carboxylate

生成物 1

HCID 70896244(S)-7-(quinuclidin-3-yl)-8,9-dihydro-[1,4]diazepino[6,7,1-hi]indazol-6(7H)-one収率 63%

実験手順

To a suspension of lithium (S)-1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indazole-7-carboxylate (360 mg, 1.1 mmol) from Step G above in THF (50 mL) was added N,N-diisopropylethylamine (1.2 mL, 6.7 mmol) and the mixture was stirred at ambient temperature for 10 min. To the above reaction mixture was added 1-propanephosphonic acid cyclic anhydride (T3P) (3.6 g, 5.6 mmol) and the reaction was stirred for 2.5 h. The reaction was quenched with saturated aqueous sodium bicarbonate (100 mL), extracted with ethyl acetate (3×250 mL), and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude solid was purified by SCX-2 resin to afford (S)-7-(quinuclidin-3-yl)-8,9-dihydro-[1,4]diazepino[6,7,1-hi]indazol-6(7H)-one (207 mg, 63%): 1H NMR (500 MHz, CD3OD) δ 8.17 (dd, J=7.5, 1.0 Hz, 1H), 8.15 (s, 1H), 8.00 (dd, J=8.0, 1.0 Hz, 1H), 7.31 (t, J=8.0 Hz, 1H), 4.80-4.75 (m, 2H), 4.70-3.80 (m 3H), 3.38-3.34 (m, 1H), 3.20-3.05 (m, 2H); 2.96-2.85 (m, 3H), 2.14-2.00 (m, 1H), 1.95-1.65 (m, 4H); MS (ESI+) m/z 297 (M+H).

後処理

  1. stirringthe reaction was stirred for 2.5 h
  2. customThe reaction was quenched with saturated aqueous sodium bicarbonate (100 mL)
  3. extractionextracted with ethyl acetate (3×250 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude solid was purified by SCX-2 resin

出典と根拠

ORDレコード
ord-14f2e9891d864287bacf250acb40a3d2
出典データセット
uspto-grants-2014_04
特許番号
US08710046B2

反応ノート

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