Potassium Phosphate, Tribasic → 4-(2-Fluoro-4-trimethylsilanylphenylamino)-indazole-1,5-dicarboxylic acid di-tert-butyl ester

HRID 79020Notes

Reaction equation

HRID 79020 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([Si:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[NH2:12].[C:13]([O:17][C:18]([N:20]1[C:28]2[C:23](=[C:24](Br)[C:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:26][CH:27]=2)[CH:22]=[N:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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].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>[C:13]([O:17][C:18]([N:20]1[C:28]2[C:23](=[C:24]([NH:12][C:3]3[CH:4]=[CH:5][C:6]([Si:8]([CH3:9])([CH3:11])[CH3:10])=[CH:7][C:2]=3[F:1])[C:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:26][CH:27]=2)[CH:22]=[N:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 575229904-Bromo-indazole-1,5-dicarboxylic acid di-tert-butyl esterHCID 595965992-Fluoro-4-(trimethylsilyl)aniline

Product 1

HCID 575231194-(2-Fluoro-4-trimethylsilanylphenylamino)-indazole-1,5-dicarboxylic acid di-tert-butyl esterYield 76.1%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 2-fluoro-4-trimethylsilanyl-phenylamine (1.2 g, 6.5 mmol) in toluene (20 mL) was added to a mixture of 4-bromo-indazole-1,5-dicarboxylic acid di-tert-butyl ester (2.0 g, 5.0 mmol), Pd2 dba3 (114 mg, 2.5 mol %), Xantphos (144 mg, 5 mol %) and potassium phosphate tribasic (1.49 g, 7 mmol) under nitrogen. The atmosphere was evacuated and back-filled with nitrogen and then the reaction mixture heated at 90° C. for 18 hours. The cooled reaction mixture was diluted with ethyl acetate, filtered through Celite®, and the filtrate concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, dry loading on HM-N, gradient 0 to 10% ethyl acetate in cyclohexane) to give the title compound as an orange gum (1.9 g, 76%). 1H NMR (CDCl3, 400 MHz) 10.03 (1H, s), 8.05 (1H, d, J=9.03 Hz), 7.57 (1H, dd, J=9.00, 0.83 Hz), 7.28-7.18 (4H, m), 1.68 (9H, s), 1.63 (9H, s), 0.28 (9H, s).

Workup

  1. customThe atmosphere was evacuated
  2. additionback-filled with nitrogen
  3. customThe cooled reaction mixture
  4. filtrationfiltered through Celite®
  5. concentrationthe filtrate concentrated in vacuo
  6. dry with materialThe resultant residue was subjected to flash chromatography (Si—PPC, dry loading on HM-N, gradient 0 to 10% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-baa62cc3e99d42abb0bfe4ff2d83bf3b
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

Loading…