Potassium Phosphate, Tribasic → 3-(2-Chloro-4-isopropyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

HRID 2264987Notes

Reaction equation

HRID 2264987 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH2:16])=[O:5])[CH3:2].[Cl:17][C:18]1[CH:23]=[C:22]([CH:24]([CH3:26])[CH3:25])[CH:21]=[CH:20][C:19]=1OS(C(F)(F)F)(=O)=O.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:16][C:19]1[CH:20]=[CH:21][C:22]([CH:24]([CH3:26])[CH3:25])=[CH:23][C:18]=1[Cl:17])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59596525HCID 59596525, compoundHCID 59596633Trifluoro-methanesulfonic acid 2-chloro-4-isopropyl-phenyl ester

Product 1

HCID 595965143-(2-Chloro-4-isopropyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 24%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A degassed solution of 3-amino-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (300 mg, 1.4 mmol), trifluoro-methanesulfonic acid 2-chloro-4-isopropyl-phenyl ester (700 mg, 2.3 mmol), Pd2dba3 (63 mg, 0.068 mmol), Xantphos (79 mg, 0.14 mmol) and K3PO4 (0.58 g, 2.7 mmol) in toluene (10 ml) was heated at 120° C. for 18 hours. The reaction mixture was cooled to ambient temperature then filtered through a pad of Celite®. The filtrate was concentrated in vacuo to give a brown gum. The gum was purified by flash chromatography (Si-SPE, DCM:EtOAc, 90:10) to provide the title compound as a yellow gum (120 mg, 24%). LCMS (method B): RT=2.82 min, M+H+=372.

Workup

  1. filtrationthen filtered through a pad of Celite®
  2. concentrationThe filtrate was concentrated in vacuo
  3. customto give a brown gum
  4. customThe gum was purified by flash chromatography (Si-SPE, DCM:EtOAc, 90:10)

Sources & evidence

ORD record
ord-31a38ff5ceba44c3a2198ed727324f94
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

Loading…