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

HRID 458415Notes

Reaction equation

HRID 458415 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[S:32][CH:31]=[C:30]([C:33](O)=[O:34])[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)[S:32][CH:31]=2)=[O:34])[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 695162095-{(9aS)-3-(ethoxycarbonyl)-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizin-4-yl}-3-thiophenecarboxylic acid

Product 1

HCID 10196902Ethyl(9aS)-4-{4-[(2,3-dihydro-1H-inden-1-ylamino)carbonyl]-2-thieny}-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-thiophenecarboxylic acid (0.100 g, 0.202 mmol) was dissolved in CH2Cl2. 1-aminoindane (0.039 mL, 0.328 mmol) was added followed by EDCI (0.047 g, 0.243 mmol) and HOBt (0.033 g, 0.243 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 3:1 EtOAc:Hexanes eluted the product to provide the title compound upon concentration as a white solid (0.085 g, 0.139 mmol, 69% yield): 1H NMR (CDCl3, 400 MHz) δ 8.08 (s, 1H), 7.46 (s, 1H), 7.35–7.31 (m, 1H), 7.28–7.20 (m, 3H), 7.16 (dd, J=8.5, 5.5 Hz, 2H), 6.97 (t, 2H), 6.17 (m, 1H), 5.67 (dd, J=15.5, 7.8 Hz, 1H), 4.69 (dd, J=10.4, 6.2 Hz, 1H), 4.19 (dd, J=14.3, 7.0 Hz, 2H), 3.76–3.69 (m, 1H), 3.42–3.36 (m, 1H), 3.19–2.99 (m, 5H), 2.96–2.87 (m, 1H), 2.74–2.64 (m, 1H), 2.51–2.43 (m, 1H), 2.39–2.27 (m, 2H), 1.96–1.86 (m, 1H), 1.41–1.34 (m, 1H), 1.09 (t, 7.0 Hz); ESMS m/z 610 (M+H)+, 608 (M−H)+; Anal. Calcd. For C35H32FN3O4S.½H2O: C, 68.44; H, 5.33; N, 6.84; found: C, 68.42; H, 5.50; N, 6.78.

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 3:1 EtOAc:Hexanes eluted the product

Sources & evidence

ORD record
ord-fd53dded186348098e6d23ba19f09476
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

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