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4-Fluorophenylboronic acid → 1-{[4-amino-2-(ethoxymethyl)-7-(4-fluorophenyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanol

HRID 598038
Notes
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Reaction equation

HRID 598038 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][O:23][CH2:24][CH3:25])[N:14]([CH2:15][C:16]3([OH:21])[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[N:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C(O)CC.O>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][O:23][CH2:24][CH3:25])[N:14]([CH2:15][C:16]3([OH:21])[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[N:8]=[CH:7][C:6]([C:31]3[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=3)=[CH:5][C:4]=2[N:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 2856454-Fluorophenylboronic acidHCID 22595341Propanol waterHCID 589707021-{[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanol

Product 1

HCID 589706931-{[4-amino-2-(ethoxymethyl)-7-(4-fluorophenyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanolYield 57%

Reagents, catalysts & solvents 4

HCID 11776
Triphenylphosphine
Catalyst
HCID 167845palladium(II) acetateCatalyst
HCID 1140TolueneSolvent
HCID 10340Sodium CarbonateSolvent

Procedure

1-{[4-Amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanol (1.13 g, 2.7 mmol), 4-fluorobenzeneboronic acid (0.43 g, 3.1 mmol), triphenylphosphine (6.3 mg, 0.024 mmol), and 5:1 (v/v) 1-propanol/water (6.6 mL) were combined under a nitrogen atmosphere. A 5 mg/mL solution of palladium (II) acetate (1.8 mg, 0.008 mmol) in toluene and aqueous sodium carbonate (1.8 mL of 2 M) were sequentially added. The reaction mixture was heated at reflux for two hours, allowed to cool to room temperature, and partitioned between chloroform (75 mL) and brine (20 mL). The organic fraction was separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue (1.27 g) was purified by trituration with acetonitrile at 98° C. followed by recrystallization from chloroform/hexane. The crystals were dried in a vacuum oven at 110 C for two hours to provide 0.67 g of 1-{[4-amino-2-(ethoxymethyl)-7-(4-fluorophenyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanol as a steel-gray solid, mp 212-212.5° C.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for two hours
  3. custompartitioned between chloroform (75 mL) and brine (20 mL)
  4. customThe organic fraction was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue (1.27 g) was purified by trituration with acetonitrile at 98° C.
  9. customfollowed by recrystallization from chloroform/hexane
  10. customThe crystals were dried in a vacuum oven at 110 C for two hours

Sources & evidence

ORD record
ord-44c5451f96b04599b2bb25a1a41b6beb
Source dataset
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07897609B2

Reaction notes

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