5-Indolylboronic acid → HCID 178510910, compound

HRID 30435Notes

Reaction equation

HRID 30435 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[NH:11])=[CH:4][CH:3]=1.[NH:20]1[C:28]2[C:23](=[CH:24][C:25](B(O)O)=[CH:26][CH:27]=2)[CH:22]=[CH:21]1>COCCOC.O.C(O)C.C([O-])(O)=O.[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:10](=[NH:11])[CH:9]=[CH:8][C:5]2[CH:6]=[CH:7][C:2]([C:25]3[CH:24]=[C:23]4[C:28](=[CH:27][CH:26]=3)[NH:20][CH:21]=[CH:22]4)=[CH:3][CH:4]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 2

HCID 27343615-Indolylboronic acidHCID 178510908HCID 178510908, compound

Product 1

HCID 178510910HCID 178510910, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 516892Sodium BicarbonateSolventHCID 86587095Dimethoxyethane ethanol waterSolvent

Procedure

A mixture of 0.075 g (0.22 mmol) of 3-(4-bromo-phenyl)-N-(4-chloro-phenyl)-acrylamidine, 0.042 g (0.26 mmol) of 5-indoleboronic acid, and 0.013 g (0.011 mmol) of Pd(PPh3)4 in 3 mL of DME/water/ethanol (4/2/1) in a sealed tube was heated under microwave (45 W, 5 min). The reaction was diluted with 10 mL of saturated NaHCO3, and extracted with three 10 mL portions of ethyl acetate. The combined organic extracts were washed with 10 mL of brine, dried over Na2SO4, filtered and concentrated. The residue was purified by preparative TLC eluting with 60% ethyl acetate in hexanes plus 1% NH4OH to give 0.036 g of N-(4-chloro-phenyl)-3-[4-(1H -indol-5-yl)-phenyl]-acrylamidine. Method M: To a stirred solution of 0.10 g (0.27 mmol) of N-(4-chloro-phenyl)-3-[4-(1H -indol-5-yl)-phenyl]-acrylamidine in 3 mL of DMF was added 0.011 g (0.28 mmol) of 60% NaH at 0° C. After 1 h, 0.018 mL (0.28 mmol) of iodomethane was introduced, the reaction was warmed to room temperature overnight and quenched with 10 mL of saturated NaHCO3. It was extracted with three 10 mL portions of dichloromethane. The combined organic extracts were washed with 10 mL of brine, dried over Na2SO4, filtered and concentrated. The residue was chromatographed eluting with 40% ethyl acetate in hexanes to give 0.028 g of N-(4-chloro-phenyl)-3-[4-(1-methyl-1H-indol-5-yl)-phenyl]-acrylamidine.

Workup

  1. temperaturewas heated under microwave (45 W, 5 min)
  2. extractionextracted with three 10 mL portions of ethyl acetate
  3. washThe combined organic extracts were washed with 10 mL of brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative TLC
  8. washeluting with 60% ethyl acetate in hexanes plus 1% NH4OH

Sources & evidence

ORD record
ord-a3360fa9808e462580515e7310f7fb65
Source dataset
uspto-grants-2008_09
Patent number
US07423149B2

Reaction notes

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