Potassium Phosphate, Tribasic → Methyl 2-amino-5-({1-[3-(2-tert-butoxy-2-oxoethoxy)phenyl]-2-methylindolizin-3-yl}carbonyl)benzoate

HRID 2273550Notes

Reaction equation

HRID 2273550 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]([C:12]([C:14]2[N:22]3[C:17]([CH:18]=[CH:19][CH:20]=[CH:21]3)=[C:16](Br)[C:15]=2[CH3:24])=[O:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:25]([O:29][C:30](=[O:48])[CH2:31][O:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=1)([CH3:28])([CH3:27])[CH3:26].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[NH2:1][C:2]1[CH:11]=[CH:10][C:9]([C:12]([C:14]2[N:22]3[C:17]([CH:18]=[CH:19][CH:20]=[CH:21]3)=[C:16]([C:37]3[CH:36]=[CH:35][CH:34]=[C:33]([O:32][CH2:31][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:48])[CH:38]=3)[C:15]=2[CH3:24])=[O:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 57500395Methyl 2-amino-5-[(1-bromo-2-methylindolizin-3-yl)carbonyl]benzoateHCID 59852416Tert-butyl 2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]acetate

Product 1

HCID 57500396Methyl 2-amino-5-({1-[3-(2-tert-butoxy-2-oxoethoxy)phenyl]-2-methylindolizin-3-yl}carbonyl)benzoateYield 77%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

The mixture of 2.78 g (7.18 mmol) of methyl 2-amino-5-[(1-bromo-2-methylindolizin-3-yl)carbonyl]benzoate (described in Patent Application WO2005028476), 3.6 g (10.8 mmol) of tert-butyl[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]acetate (CAS 769968-18-5; described in Patent Application WO2004084813), 0.73 g (1.0 mmol) of PdCl2(dppf) in 22 ml of a molar solution of potassium phosphate and 100 ml of 1,2-dimethoxyethane is heated at 100° C. under argon. After 2 hours and 4 hours, a further 100 mg of PdCl2(dppf) are added. After 6 hours at 100° C. under argon, the reaction medium is allowed to return to ambient temperature and is then filtered. The organic solution is washed with water and with a saturated solution of sodium chloride, dried over sodium sulphate and concentrated to dryness. The residue obtained is purified by flash chromatography on silica gel (dichloromethane/diisopropyl ether gradient=100/0 to 0/100), to give 2.84 g (77%) of a yellow powder.

Workup

  1. waitAfter 6 hours at 100° C. under argon
  2. customto return to ambient temperature
  3. filtrationis then filtered
  4. washThe organic solution is washed with water and with a saturated solution of sodium chloride
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated to dryness
  7. customThe residue obtained
  8. customis purified by flash chromatography on silica gel (dichloromethane/diisopropyl ether gradient=100/0 to 0/100)

Sources & evidence

ORD record
ord-7c8062c0d37e4a49aaa11dda48e9275f
Source dataset
uspto-grants-2015_09
Patent number
US09120819B2

Reaction notes

Loading…