2-Fluoro-4-iodoaniline → 7-Fluoro-8-(2-fluoro-4-iodophenylamino)-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylic acid

HRID 910155Notes

Reaction equation

HRID 910155 reaction equation
Cl[C:2]1[C:11]([C:12]([OH:14])=[O:13])=[C:10]2[N:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[C:4](=[O:15])[C:3]=1[F:16].[F:17][C:18]1[CH:24]=[C:23]([I:25])[CH:22]=[CH:21][C:19]=1[NH2:20].C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>C1COCC1>[F:16][C:3]1[C:4](=[O:15])[N:5]2[C:10](=[C:11]([C:12]([OH:14])=[O:13])[C:2]=1[NH:20][C:19]1[CH:21]=[CH:22][C:23]([I:25])=[CH:24][C:18]=1[F:17])[CH2:9][CH2:8][CH2:7][CH2:6]2

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 576898038-Chloro-7-fluoro-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylic acid

Product 1

HCID 576898117-Fluoro-8-(2-fluoro-4-iodophenylamino)-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylic acidYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

8-Chloro-7-fluoro-6-oxo-2,3,4,6-tetrahydro-1H-quinolizine-9-carboxylic acid (7d, 426 mg, 1.74 mmol, 1 eq) and 2-fluoro-4-iodoaniline (827 mg, 3.49 mmol, 2 eq) were mixed in anhydrous THF (10 ml) at 0° C. under N2. 1N lithium hexamethyldisilazide in THF (5.23 ml, 5.23 mmol, 3 eq) was added drop wise and the mixture stirred for 4 hours while allowing the temperature to return to RT. The solution was evaporated and purified by flash chromatography using 10-16% MeOH in DCM as eluent. This afforded the title compound as a tan solid (216 mg, 28%). [M+H] calc'd for C16H13F2IN2O3, 447. found, 447.

Workup

  1. customto return to RT
  2. customThe solution was evaporated
  3. custompurified by flash chromatography

Sources & evidence

ORD record
ord-2ff038de13f04575bf5640253b0520a7
Source dataset
uspto-grants-2011_09
Patent number
US08022057B2

Reaction notes

Loading…