1,2-Dichloroethane → Ethyl (9aS)-2-(2,4-difluorobenzyl)-4-(4-{[(2-furylmethyl)amino]carbonyl}phenyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

HRID 458405Notes

Reaction equation

HRID 458405 reaction equation
[F:1][C:2]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:3]=1[CH2:4][C:5]1[C:6]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[C:7]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=2)[C:8]2[C:15](=[O:16])[N:14]3[C@@H:10]([CH2:11][CH2:12][CH2:13]3)[C:9]=2[N:17]=1.[CH:37]1[CH:41]=[C:40]([CH2:42][NH2:43])[O:39][CH:38]=1.C(Cl)CCl>C(Cl)Cl.CCOC(C)=O>[F:1][C:2]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:3]=1[CH2:4][C:5]1[C:6]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[C:7]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([NH:43][CH2:42][C:40]3[O:39][CH:38]=[CH:37][CH:41]=3)=[O:24])=[CH:20][CH:19]=2)[C:8]2[C:15](=[O:16])[N:14]3[C@@H:10]([CH2:11][CH2:12][CH2:13]3)[C:9]=2[N:17]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 3438FurfurylamineHCID 697417474-[(9aS)-2-(2,4-Difluorobenzyl)-3-(ethoxycarbonyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizin-4-yl]benzoic acid

Product 1

HCID 86598164Ethyl (9aS)-2-(2,4-difluorobenzyl)-4-(4-{[(2-furylmethyl)amino]carbonyl}phenyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylateYield 59%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-[(9aS)-2-(2,4-Difluorobenzyl)-3-(ethoxycarbonyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-α]pyrrolizin-4-yl]benzoic acid (0.120 g, 0.244 mmol) was dissolved in 2 mL DCM. 2-Furfurylamine (0.035 g, 0.365 mmol) was added followed by EDC (0.070 g, 0.365 mmol). After 3 h, the reaction mixture was diluted with EtOAc and washed with pH 4.0 buffer (3×), saturated NaHCO3, brine, and dried over MgSO4. Purification on SiO2 (hexanes:EtOAc 1:1 to 1:2) provided the title compound as a white solid (0.082 g, 0.14 mmol, 59%): 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=8.0 Hz, 2H), 7.43 (d, J=8.0 Hz, 2H), 7.17 (m, 1H), 6.78 (m, 2H), 6.43 (t, J=5.2 Hz, 1H), 6.34 (m, 1H), 6.30 (m, 1H), 4.69 (dd, J=12.4, 6.4 Hz, 1H), 4.64 (d, J=5.6 Hz, 2H), 4.31 (AB, J=15.6, 2H), 3.90 (dq, J=7.2, 2.0 Hz, 2H), 3.68 (m, 1H), 3.35 (m, 1H), 2.45 (m, 1H), 2.30 (m, 2H), 1.38 (m, 1H), 0.85 (t, J=7.2 Hz, 3H) ppm. ESMS m/z 572 (M+H)+, 604 (M+Na)+. Anal. calcd. for C32H27F2N3O5.¼H2O: C, 66.72; H, 4.81; N, 7.29; found: C, 66.70; H, 4.70; N, 7.21.

Workup

  1. washwashed with pH 4.0 buffer (3×), saturated NaHCO3, brine
  2. dry with materialdried over MgSO4
  3. customPurification on SiO2 (hexanes:EtOAc 1:1 to 1:2)

Sources & evidence

ORD record
ord-c038283e41e24ea2b203015313c7cca2
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

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