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

HRID 853905Notes

Reaction equation

HRID 853905 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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].

Workup

  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)

Sources & evidence

ORD record
ord-751b90322b3845f6a24e1f72fcf29698
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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