Hydrochloric Acid → Ethyl(9aS)-4-{4-[(2,3-dihydro-1H-inden-1-ylamino)carbonyl]-2-furyl}-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

HRID 458419Notes

Reaction equation

HRID 458419 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:18]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[N:17][C:9]2[C@H:10]3[N:14]([C:15](=[O:16])[C:8]=2[C:7]=1[C:28]1[O:32][CH:31]=[C:30]([C:33]([OH:35])=O)[CH:29]=1)[CH2:13][CH2:12][CH2:11]3)=[O:5])[CH3:2].[NH2:36][CH:37]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH2:39][CH2:38]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl>C(Cl)Cl>[CH:37]1([NH:36][C:33]([C:30]2[CH:29]=[C:28]([C:7]3[C:8]4[C:15](=[O:16])[N:14]5[C@H:10]([C:9]=4[N:17]=[C:18]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[C:6]=3[C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:11][CH2:12][CH2:13]5)[O:32][CH:31]=2)=[O:35])[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH2:39][CH2:38]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 123445(+-)-1-AminoindanHCID 695165845-{(9aS)-3-(ethoxycarbonyl)-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizin-4-yl}-3-furoic acid

Product 1

HCID 10153217Ethyl(9aS)-4-{4-[(2,3-dihydro-1H-inden-1-ylamino)carbonyl]-2-furyl}-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-{(9aS)-3-(ethoxycarbonyl)-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizin-4-yl}-3-furoic acid (0.100 g, 0.209 mmol) was dissolved in CH2Cl2. 1-aminoindane (0.037 mL, 0.313 mmol) was added followed by EDCI (0. 048 g, 0.251 mmol) and HOBt (0.034 g, 0.251 mmol). After 14 h of stirring at ambient temperature the reaction mixture was poured onto 5% HCl solution and extracted with CH2Cl2. The organics were washed with sat'd NaHCO3, brine and then dried (Na2SO4), filtered and concentrated to a brown residue. Chromatography on silica gel using 4:1 EtOAc:Hexanes eluted the product to provide the title compound upon concentration as a white solid (0.062 g, 0.105 mmol, 50% yield): 1H NMR (CDCl3, 400 MHz) δ 8.12 (s, 1H), 8.11 (d, J=9.5 Hz, 1H), 7.32 (m, 1H), 7.25–7.15 (m, 5H), 6.96 (t, J=8.6 Hz, 2H), 6.32 (m, 1H), 5.69 (dd, J=15.5, 7.7 Hz, 1H), 4.65 (dd, J=10.4, 6.2 Hz, 1H), 4.37 (dd, J=14.2, 7.0), 3.73–3.63 (m, 1H), 3.44–3.38 (m, 1H), 3.17–3.01 (m, 5H), 2.92–2.83 (m, 1H), 2.68–2.60 (m, 1H), 2.48–2.40 (m,1H), 2.37–2.25 (m, 2H), 1.96–1.86 (m, 1H), 1.38–1.30 (m, 1H), 1.27 (t, J=7.1 Hz, 3H); ESMS m/z 594 (M+H)+, 592 (M−H)+; Anal. Calcd. For C35H32FN3O5.½H2O: C, 69.75; H, 5.52; N, 6.97; found: C, 69.58; H, 5.43; N, 7.05.

Workup

  1. extractionextracted with CH2Cl2
  2. washThe organics were washed with sat'd NaHCO3, brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to a brown residue
  6. washChromatography on silica gel using 4:1 EtOAc:Hexanes eluted the product

Sources & evidence

ORD record
ord-8283b75691da49fda94cc3ac2dc5bb87
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

Loading…