Water → HCID 72201438, compound

HRID 629112Notes

Reaction equation

HRID 629112 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][N:21]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].[CH3:22][O:23][C:24]1(B(O)O)[N:29]=[CH:28][CH:27]=[CH:26][NH:25]1.C([O-])([O-])=O.[Na+].[Na+].O>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.COCCOC.CCO>[CH3:22][O:23][C:24]1[N:29]=[CH:28][C:27]([C:2]2[CH:3]=[C:4]([CH:19]=[CH:20][N:21]=2)[C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=2)=[O:6])=[CH:26][N:25]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 89906627HCID 89906627, compoundHCID 131735362HCID 131735362, compound

Product 1

HCID 72201438HCID 72201438, compound

Reagents, catalysts & solvents 3

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

Procedure

2-Bromo-N-(4-(trifluoromethoxy)phenyl)isonicotinamide (Stage 69.1, 70 mg, 0.194 mmol), 2-methoxypyrimidine boronic acid (45 mg, 0.291 mmol), Pd(PPh3)2Cl2 (5.44 mg, 7.75 μmol), Na2CO3 (71.9 mg, 0.678 mmol), water (194 μL), EtOH (129 μL) and DME (969 μL) were added to a vial, which was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 20 min. The RM was stirred with Si-Thiol (53.8 mg, 0.078 mmol) for 30 min. The resin was filtered off and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (Biotage Silica gel column, 4 g, DCM/MeOH+1% NH4OH from 1.5% to 20% MeOH+1% NH4OH) to yield the title compound as an off-white solid. UPLC-MS (Condition 1) tR 2.58 min, m/z=391[M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 4.01 (s, 3H) 7.42 (d, J=8.56 Hz, 2H) 7.84 (dd, J=5.01, 1.35 Hz, 1H) 7.90 (m, J=9.30 Hz, 2H) 8.46 (s, 1H) 8.89 (d, J=5.14 Hz, 1H) 9.34 (s, 2H) 10.71 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. customsubjected to MW irradiation at 125° C. for 20 min
  4. filtrationThe resin was filtered off
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by flash chromatography (Biotage Silica gel column, 4 g, DCM/MeOH+1% NH4OH from 1.5% to 20% MeOH+1% NH4OH)

Sources & evidence

ORD record
ord-3aa98af644bb45d0aac6d66e9af82ce7
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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