Triethylamine → 3,3-Dimethyl-8-{[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]carbonyl}-3,4-dihydropyrimido[1,2-a]indol-10(2H)-one

HRID 853905ノート

反応式

HRID 853905 の反応式
[CH3:1][C:2]1([CH3:23])[CH2:22][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([C:19]([OH:21])=O)=[CH:11][C:12]=3[C:13]3(OCCC[O:14]3)[C:5]2=[N:4][CH2:3]1.[O:24]([CH2:31][C@@H:32]1[CH2:36][CH2:35][CH2:34][NH:33]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>C(Cl)Cl>[CH3:1][C:2]1([CH3:23])[CH2:22][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([C:19]([N:33]4[CH2:34][CH2:35][CH2:36][C@H:32]4[CH2:31][O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:21])=[CH:11][C:12]=3[C:13](=[O:14])[C:5]2=[N:4][CH2:3]1

参加物

7

反応物 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 9855629(2S)-2-(phenoxymethyl)pyrrolidineHCID 116238363',3'-dimethyl-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indole]-8'-carboxylic acid

生成物 1

HCID 115897753,3-Dimethyl-8-{[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]carbonyl}-3,4-dihydropyrimido[1,2-a]indol-10(2H)-one収率 20%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 3′,3′-dimethyl-3′,4′-dihydro-2′H-spiro[1,3-dioxane-2,10′-pyrimido[1,2-a]indole]-8′-carboxylic acid (0.090 g, 0.284 mmol) in CH2Cl2 (7 mL) was added (2S)-2-(phenoxymethyl)pyrrolidine (0.75 g, 0.427 mmol), DCC (0.082 g, 0.039 mmol), HOBT (0.038 g, 0.281 mmol) and Et3N (0.045 mL, 0.277 mmol) and the solution stirred overnight at rt. The reaction was filtered through 1 cm of silica gel washing with EtOAc. The filtrate was dried over Na2SO4, filtered, concentrated and purified on silica gel eluting with acetone/hexane (30/70). The resulting white foam was dissolved in CH2Cl2 (1.5 mL) and methanesulfonic acid (1 mL) was added and the solution was stirred at rt overnight. The reaction was poured onto ice, basified to pH 11 with ammonium hydroxide and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered, concentrated and purified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (35/65) to give the title compound as a yellow foam (0.021 g, 20%). NMR (400 Mz, DMSO-d6): consistent. MS (ES+) m/z 418.3 [M+H].

後処理

  1. filtrationThe reaction was filtered through 1 cm of silica gel washing with EtOAc
  2. dry with materialThe filtrate was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified on silica gel eluting with acetone/hexane (30/70)
  6. dissolutionThe resulting white foam was dissolved in CH2Cl2 (1.5 mL)
  7. additionmethanesulfonic acid (1 mL) was added
  8. stirringthe solution was stirred at rt overnight
  9. additionThe reaction was poured onto ice
  10. extractionextracted with EtOAc (3×)
  11. dry with materialThe combined organic extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. custompurified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (35/65)

出典と根拠

ORDレコード
ord-751b90322b3845f6a24e1f72fcf29698
出典データセット
uspto-grants-2007_08
特許番号
US07256198B2

反応ノート

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