Potassium Phosphate, Tribasic → 2-[3-Pyridin-2-ylethynyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazol-6-ylamino]-benzoic acid methyl ester

HRID 1827479Notes

Reaction equation

HRID 1827479 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]#[C:8][C:9]1[C:17]2[C:12](=[CH:13][C:14]([NH2:18])=[CH:15][CH:16]=2)[N:11]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:10]=1.BrC[C:29]1[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=1[C:31]([O-:33])=[O:32].[C:38]1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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].C(COC)OC>[CH3:38][O:33][C:31](=[O:32])[C:30]1[CH:34]=[CH:35][CH:36]=[CH:37][C:29]=1[NH:18][C:14]1[CH:13]=[C:12]2[C:17]([C:9]([C:8]#[C:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[N:10][N:11]2[CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:24])([CH3:26])[CH3:25])=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 4739258HCID 4739258, compoundHCID 235778473-Pyridin-2-ylethynyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazol-6-ylamine

Product 1

HCID 235778602-[3-Pyridin-2-ylethynyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazol-6-ylamino]-benzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-Pyridin-2-ylethynyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazol-6-ylamine (560 mg, 1.54 mmol), 2-bromomethylbenzoate (647.5 μL, 4.61 mmol), biphenyl-2-yl-dicyclohexyl-phosphane (107.8 mg, 0.308 mmol), Pd2(dba)3 (70.5 mg, 0.0768 mmol), K3PO4 (816 mg, 3.844 mmol), and dimethoxyethane (1.7 ml), were vacuum flushed with nitrogen, then heated in an oil bath at 70 degrees C. for 24 h. The black mixture was diluted with methylene chloride, and filtered, concentrated, and chromatographed (20% to 40% ethylacetate/hexanes). Yield of yellow/orange oil was 260 mg, 35% for three steps.

Workup

  1. customflushed with nitrogen
  2. additionThe black mixture was diluted with methylene chloride
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customchromatographed (20% to 40% ethylacetate/hexanes)

Sources & evidence

ORD record
ord-486fec25177a4cb0b8bc85373611b181
Source dataset
uspto-grants-2006_05
Patent number
US07053107B2

Reaction notes

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