3-Pyridinylboronic acid → HCID 22136483, compound

HRID 1827273Notes

Reaction equation

HRID 1827273 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:19]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)([C:21]3[N:25]([CH3:26])[CH:24]=[N:23][CH:22]=3)[OH:20])[CH:8]=2)[N:3]=1.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.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>[Cl:18][C:14]1[CH:13]=[C:12]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([C:19]([C:27]4[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][CH:32]=4)([C:21]4[N:25]([CH3:26])[CH:24]=[N:23][CH:22]=4)[OH:20])[CH:8]=3)[N:3]=[C:2]([C:36]3[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=3)[N:11]=2)[CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 2

HCID 27343783-Pyridinylboronic acidHCID 22136471HCID 22136471, compound

Product 1

HCID 22136483HCID 22136483, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 2-chloro-4-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-6-quinazolinemethanol (0.0051 mol), described in International Patent Specification WO 00/39082, 3-pyridinyl-boronic acid (0.0077 mol) and Pd(PPh3)2Cl2 (0.001 mol) in sodium carbonate 2M (25 ml) and dioxane (25 ml) was stirred at 115° C. for 3 hours, then cooled, poured out into ice water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.1; 15–40 μm). The pure fractions were collected and the solvent was evaporated, yielding 1.02 g of a fraction which was crystallized from CH3CN. The precipitate was filtered off and dried, yielding 0.7 g (36%) of 4-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-2-(3-pyridinyl)-6-quinazolinemethanol, mp.178° C.

Workup

  1. temperaturecooled
  2. extractionextracted with DCM
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.1; 15–40 μm)
  8. customThe pure fractions were collected
  9. customthe solvent was evaporated
  10. customyielding 1.02 g of a fraction which
  11. customwas crystallized from CH3CN
  12. filtrationThe precipitate was filtered off
  13. customdried

Sources & evidence

ORD record
ord-649c292bea174ad9bd9a2b634d847dde
Source dataset
uspto-grants-2006_05
Patent number
US07053105B2

Reaction notes

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