1,2-Dimethoxyethane → 1-[3-(5-Fluoropyridin-3-yl)phenyl]-1-pyridin-4-yl-1H-isoindol-3-amine

HRID 2264729Notes

Reaction equation

HRID 2264729 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:17])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[F:24][C:25]1[CH:26]=[N:27][CH:28]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:30]=1.C(=O)([O-])[O-].[K+].[K+].C(COC)OC>C(O)C.O>[F:24][C:25]1[CH:30]=[C:29]([C:2]2[CH:3]=[C:4]([C:8]3([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[C:10]([NH2:17])=[N:9]3)[CH:5]=[CH:6][CH:7]=2)[CH:28]=[N:27][CH:26]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 164142683-Fluoro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 595962471-(3-Bromophenyl)-1-pyridin-4-yl-1H-isoindol-3-amine

Product 1

HCID 595962541-[3-(5-Fluoropyridin-3-yl)phenyl]-1-pyridin-4-yl-1H-isoindol-3-amineYield 54%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 1-(3-bromophenyl)-1-pyridin-4-yl-1H-isoindol-3-amine (Scheme #9, C) (0.073 g, 0.20 mmol), 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.067 g, 0.30 mmol), potassium carbonate (0.055 g, 0.40 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (0.020 g, 0.025 mmol), dimethoxyethane (2 mL), water (1 mL) and ethanol (0.3 mL) under an argon atmosphere was irradiated in a microwave at 100° C. for 15 min. The reaction mixture was filtered and partitioned between water and ethyl acetate, the organic phase was concentrated and the residue was purified by preparative HPLC, which gave the title compound (0.041 g, 54%). 1H NMR (DMSO-d6) δ 8.67-8.63 (m, 1 H), 8.57 (d, J=2.78 Hz, 1 H), 8.49-8.42 (m, 2 H), 7.99-7.90 (m, 2 H), 7.85-7.79 (m, 1 H), 7.67-7.62 (m, 2 H), 7.55-7.41 (m, 4 H), 7.37-7.28 (m, 2 H), 6.95 (br s, 2 H), 1.91 (s, 2.2 H); MS (ESI) m/z 381 [M+1]+.

Workup

  1. customwas irradiated in a microwave at 100° C. for 15 min
  2. filtrationThe reaction mixture was filtered
  3. custompartitioned between water and ethyl acetate
  4. concentrationthe organic phase was concentrated
  5. customthe residue was purified by preparative HPLC, which

Sources & evidence

ORD record
ord-9b2e74a7eee94740ad0d05f2ca96fd20
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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