Potassium Phosphate, Tribasic → [3-Hydroxy-5-(1H-indol-4-YL)-phenyl]-(6-hydroxymethyl-pyridin-3-YL)-methanone

HRID 1784821Notes

Reaction equation

HRID 1784821 reaction equation
COC1C=CC(C[O:8][C:9]2[CH:10]=[C:11]([CH:25]=[C:26]([C:28]3[CH:36]=[CH:35][CH:34]=[C:33]4[C:29]=3[CH:30]=[CH:31][N:32]4[Si](C(C)C)(C(C)C)C(C)C)[CH:27]=2)[C:12]([C:14]2[CH:15]=[CH:16][C:17]([CH2:20][O:21]C(=O)C)=[N:18][CH:19]=2)=[O:13])=CC=1.BrC1C=C(C=C(OCC2C=CC(OC)=CC=2)C=1)C(C1C=CC(COC(=O)C)=NC=1)=O.CC1(C)C(C)(C)OB(C2C=CC=C3C=2C=CN3[Si](C(C)C)(C(C)C)C(C)C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(Cl)Cl.Cl[Pd-](P(C1CC2CC1CC2)C1CC2CC1CC2)C1C=CC=CC=1C1C=CC=CC=1N(C)C>[OH:8][C:9]1[CH:10]=[C:11]([C:12]([C:14]2[CH:19]=[N:18][C:17]([CH2:20][OH:21])=[CH:16][CH:15]=2)=[O:13])[CH:25]=[C:26]([C:28]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:29]=2[CH:30]=[CH:31][NH:32]3)[CH:27]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27955744-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1-(triisopropylsilyl)-1H-indoleHCID 68844868Acetic acid 5-[3-(4-methoxy-benzyloxy)-5-(1-triisopropylsilanyl-1H-indol-4-yl)-benzoyl]-pyridin-2-ylmethyl esterHCID 68844896Acetic acid 5-[3-bromo-5-(4-methoxy-benzyloxy)-benzoyl]-pyridin-2-ylmethyl ester

Product 1

HCID 15604424[3-Hydroxy-5-(1H-indol-4-YL)-phenyl]-(6-hydroxymethyl-pyridin-3-YL)-methanone

Reagents, catalysts & solvents 3

HCID 178482708HCID 178482708, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Acetic acid 5-[3-(4-methoxy-benzyloxy)-5-(1-triisopropylsilanyl-1H-indol-4-yl)-benzoyl]-pyridin-2-ylmethyl ester. To the mixture of acetic acid 5-[3-bromo-5-(4-methoxy-benzyloxy)-benzoyl]-pyridin-2-ylmethyl ester (145 mg, 0.308 mmol) and chloro(di-2-norbornylphosphino)(2′dimethylamino-1,1′-biphenyl-2-yl)palladium (II) (15 mg) in dioxane (6 mL) under nitrogen was added a solution of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-triisopropylsilanyl-1H-indole (129 mg, 0.324 mmol) in dioxane (6 mL), followed by 2M K3PO4 (0.3 mL, 0.6 mmol). The resulting solution was heated at reflux for 24 hr. The reaction mixture was then diluted with methylene chloride and the organic phase washed with brine, dried, and concentrated. After removal of the solvents, the crude product was purified by flash chromatography (3:1 hexane/EtOAc) to afford the titled product which was carried to the next step without further purification.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureat reflux for 24 hr
  3. washthe organic phase washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customAfter removal of the solvents
  7. customthe crude product was purified by flash chromatography (3:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-6703728128714fcc8e5ef29e680462c9
Source dataset
uspto-grants-2009_03
Patent number
US07504401B2

Reaction notes

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