Hydrochloric Acid → (8bS)-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-7-[2-(4-fluorophenyl)ethyl]-6,13-dioxo-5,8b,9,10,11,13-hexahydro-6H-benzo[c]pyrrolizino[2,1-f][2,7]naphthyridine-3-carboxamide

HRID 458478Notes

Reaction equation

HRID 458478 reaction equation
[C@H:1]1([NH:10][C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:24]4[C:25](=[O:31])[N:26]5[C@H:30]([C:23]=4[N:22]=[C:21]([CH2:32][CH2:33][C:34]4[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=4)[C:20]=3[C:41](OCC)=[O:42])[CH2:29][CH2:28][CH2:27]5)=[C:15]([N+:46]([O-])=O)[CH:14]=2)=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C(O)C.S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl>O>[C@H:1]1([NH:10][C:11]([C:13]2[CH:18]=[CH:17][C:16]3[C:19]4[C:24]5[C:25](=[O:31])[N:26]6[C@H:30]([C:23]=5[N:22]=[C:21]([CH2:32][CH2:33][C:34]5[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=5)[C:20]=4[C:41](=[O:42])[NH:46][C:15]=3[CH:14]=2)[CH2:29][CH2:28][CH2:27]6)=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 24489Sodium DithioniteHCID 86598178Ethyl (9aS)-4-(4-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}-2-nitrophenyl)-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

Product 1

HCID 69516247(8bS)-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-7-[2-(4-fluorophenyl)ethyl]-6,13-dioxo-5,8b,9,10,11,13-hexahydro-6H-benzo[c]pyrrolizino[2,1-f][2,7]naphthyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of ethyl (9aS)-4-(4-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}-2-nitrophenyl)-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate Example 53 (0.068 g, 0.11 mmol, 1 equiv) in a 1:1 mixture of ethanol and H2O (4.0 mL) was treated with sodium dithionite (0.057 g, 0.33 mmol, 3 equiv). After 12 h, the reaction was acidified with 1 N HCl to ca. pH 5. Extraction with EtOAc (3×3 mL) was followed by drying (Na2SO4), and concentration. Trituration with acetone gave 0.048 g (80%) of analytically pure title compound as a light brown solid: 1H NMR (DMSO-d6, 400 MHz) δ 10.80 (s, 1H); low resolution MS (ES+) m/e 573 (MH+); RP-HPLC (Dynamax C-18 25 cm×4.1 mm; 50–100% CH3CN in H2O with 0.1% TFA buffer; 30 minutes; 1 mL/min) tr=11.39 min, 97% purity.

Workup

  1. extractionExtraction with EtOAc (3×3 mL)
  2. customby drying
  3. concentration(Na2SO4), and concentration

Sources & evidence

ORD record
ord-e95c39bb8a0246ea80934b8eb528a657
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

Loading…