Water → HCID 89906673, compound

HRID 923946Notes

Reaction equation

HRID 923946 reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][C:3]=1I.[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.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.CCO>[Br:1][C:2]1[CH:21]=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][C:3]=1[C:27]1[CH:28]=[N:23][CH:24]=[N:25][CH:26]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acid2×HCID 89906996HCID 89906996, compound

Product 1

HCID 89906673HCID 89906673, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

4-Bromo-3-iodo-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 117.2, 3 g, 6.17 mmol), pyrimidin-5-ylboronic acid (841 mg, 6.79 mmol), Pd(PPh3)2Cl2 (217 mg, 0.309 mmol) and Na2CO3 (1.963 g, 18.52 mmol) in a mixture of DME (17.28 mL), water (4.94 mL), EtOH (2.469 mL) was degassed and stirred at 80° C. for 23 h under argon. Additional pyrimidin-5-ylboronic acid (76 mg, 0.613 mmol) was added to the RM and stirring was continued for 5 h. The RM was treated with Si-Thiol (Silicycle, 1.27 mmol/g, 1.215 g, 1.543 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (Silica gel column, 80 g, cyclohexane/EtOAc, from 10% to 45% EtOAc) to yield the title compound as a white crystalline solid. UPLC-MS (condition 1) tR=2.80 min, m/z=437.9-439.9 [M+H]+, m/z=436.0-438.0 [M−H]−.

Workup

  1. customwas degassed
  2. stirringstirring
  3. waitwas continued for 5 h
  4. filtrationfiltered
  5. customthe filtrate was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by flash chromatography (Silica gel column, 80 g, cyclohexane/EtOAc, from 10% to 45% EtOAc)

Sources & evidence

ORD record
ord-d4d0305ff1ca4e879880d0c08bfd47ef
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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