Potassium Phosphate, Tribasic → HCID 24875147, compound

HRID 2264721Notes

Reaction equation

HRID 2264721 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:18]2[CH:23]=[CH:22][C:21]([O:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:20][CH:19]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[C:13](Br)[CH:12]=2)[N:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[N:37]1[CH:42]=[CH:41][CH:40]=[C:39](B(O)O)[CH:38]=1.[Al]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC.O.C(O)C>[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:18]2[CH:23]=[CH:22][C:21]([O:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:20][CH:19]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:39]3[CH:38]=[N:37][CH:42]=[CH:41][CH:40]=3)[CH:12]=2)[N:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 5359268AluminumHCID 24875149HCID 24875149, compound

Product 1

HCID 24875147HCID 24875147, compoundYield 63.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Procedure

To methanesulfonic acid 4-[3-amino-1-(3-bromo-phenyl)-1H-isoindol-1-yl]-phenyl ester (Scheme #6, U) (100 mg, 0.18 mmol)) was added potassium phosphate (112 mg, 0.53 mmol), 3-pyridyl boronic acid (33 mg, 0.26 mmol), dichlorobis(triphenylphosphine)palladium(II) (12 mg, 0.018 mmol) and 1,2-dimethoxyethane: water:ethanol (7:3:2, 3.0 mL). The reaction was heated in an aluminium block at 100° C. for 15 minutes. The mixture was filtered through a syringe filter and the filtrate was removed of solvent under reduced pressure. The resulting residue was dissolved in acetonitrile/water with trifluoroacetic acid, (75:25:0.1, 4 mL), and purified using RP-HPLC AG2 (tR=10.6 min). The combined purified fractions were lyophilized to give the title compound (52.3 mg, 59%). 1H NMR (500 MHz, DMSO-d6/TFA-d) δ 9.23 (d, J=1.6 Hz, 1 H), 8.96 (d, J=5.6 Hz, 1 H), 8.87 (d, J=8.2 Hz, 1 H), 8.37 (d, J=7.8 Hz, 1 H), 8.17 (dd, J=8.2, 5.7 Hz, 1 H), 8.02 (d, J=7.9 Hz, 1 H), 7.90 (dd, J=18.6, 7.8 Hz, 2 H), 7.82 (s, 1 H), 7.77 (t, J=7.6 Hz, 1 H), 7.67 (t, J=7.8 Hz, 1 H), 7.56 (d, J=8.2 Hz, 1 H), 7.41 (s, 4 H), 3.39 (s, 3 H); MS (ES+) m/z 456 [M+1]+; tR=1.42 min.

Workup

  1. filtrationThe mixture was filtered through a syringe
  2. filtrationfilter
  3. customthe filtrate was removed of solvent under reduced pressure
  4. dissolutionThe resulting residue was dissolved in acetonitrile/water with trifluoroacetic acid, (75:25:0.1, 4 mL),
  5. custompurified
  6. customThe combined purified fractions

Sources & evidence

ORD record
ord-ec3f1c572cb24f7da4109b7df5b79dec
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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