3-(2-Methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine → [2-(3-{2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-ureido)-ethyl]-methyl-carbamic acid tert-butyl ester

HRID 2234676Notes

Reaction equation

HRID 2234676 reaction equation
[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:9][CH2:10][NH:11][C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18](Br)=[CH:17][C:16]=1[C:22](=[O:26])[N:23]([CH3:25])[CH3:24])=[O:13])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH3:28][O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36]1[C:44]2[C:39](=[N:40][CH:41]=[C:42](B3OC(C)(C)C(C)(C)O3)[CH:43]=2)[N:38]([S:54]([C:57]2[CH:62]=[CH:61][C:60]([CH3:63])=[CH:59][CH:58]=2)(=[O:56])=[O:55])[CH:37]=1>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].O1CCCC1>[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:9][CH2:10][NH:11][C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:42]2[CH:43]=[C:44]3[C:36]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=4[O:29][CH3:28])=[CH:37][N:38]([S:54]([C:57]4[CH:58]=[CH:59][C:60]([CH3:63])=[CH:61][CH:62]=4)(=[O:56])=[O:55])[C:39]3=[N:40][CH:41]=2)=[CH:17][C:16]=1[C:22](=[O:26])[N:23]([CH3:25])[CH3:24])=[O:13])[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 160390673-(2-Methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 57731600{2-[3-(4-Bromo-2-dimethylcarbamoyl-phenyl)-ureido]-ethyl}-methyl-carbamic acid tert-butyl ester

Product 1

HCID 57731465[2-(3-{2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-ureido)-ethyl]-methyl-carbamic acid tert-butyl esterYield 67.5%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture of {2-[3-(4-bromo-2-dimethylcarbamoyl-phenyl)-ureido]-ethyl}-methyl-carbamic acid tert-butyl ester (75 mg, 0.17 mmol), 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (85 mg, 0.168 mmol), and [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) dichloromethane adduct (13.7 mg) was dissolved in a mixture of acetonitrile (4 mL), 1 M aqueous sodium carbonate (4 mL) and tetrahydrofuran (1 mL). The mixture was irradiated in the microwave to 120° C. for 10 minutes. The reaction mixture was then concentrated and the residue was partitioned between dichloromethane and water. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography on silica gel (0 to 100% [10% methanol in ethyl acetate] in hexanes) to give 84 mg (66%) of [2-(3-{2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-ureido)-ethyl]-methyl-carbamic acid tert-butyl ester. MS: m/z 741.5 (M+H+).

Workup

  1. customThe mixture was irradiated in the microwave to 120° C. for 10 minutes
  2. concentrationThe reaction mixture was then concentrated
  3. customthe residue was partitioned between dichloromethane and water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (0 to 100% [10% methanol in ethyl acetate] in hexanes)

Sources & evidence

ORD record
ord-fec8ac998fe34284b0f77499ff79cdeb
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

Loading…