Sodium Carbonate → HCID 72201877, compound

HRID 629086Notes

Reaction equation

HRID 629086 reaction equation
Br[C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].C[O-].[Na+].[N:26]1[CH:31]=[C:30](B(O)O)[CH:29]=[N:28][CH:27]=1.[C:35]([O-])([O-])=[O:36].[Na+].[Na+]>CO.C1COCC1.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.O>[CH3:35][O:36][C:3]1[C:2]([C:30]2[CH:31]=[N:26][CH:27]=[N:28][CH:29]=2)=[CH:21][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)=[O:8])=[CH:5][N:4]=1

Participants

11

Reactant 4

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 10942334Sodium MethoxideHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 72201877HCID 72201877, compound

Reagents, catalysts & solvents 6

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 44.2, 60 mg, 0.152 mmol) and NaOMe (24.58 mg, 0.455 mmol) in anhydrous MeOH (250 μL) was stirred for 2 h at 80° C. in a sealed MW vial. Pyrimidin-5-ylboronic acid (56.4 mg, 0.455 mmol), Pd(PPh3)2Cl2 (10.65 mg, 0.015 mmol), Na2CO3 (80 mg, 0.758 mmol), water (160 μL) and EtOH (80 μL) and DME (600 μL) were added, and the vial was resealed and the RM stirred at 80° C. for 16 h. The RM was diluted with 3 mL of THF and stirred with Si-Thiol (59.7 mg, 0.076 mmol) for a 2 h and the combined filtrates were evaporated to dryness under reduced pressure. The residue was purified by flash chromatography (RediSep® Silica gel column, 4 g, DCM/MeOH+1% NH4OH from 1% to 10% MeOH+1% NH4OH) and preparative HPLC (Condition 8, 30% for 0.2 min then 30% to 60% in 12 min) to afford the title compound as a white solid. UPLC-MS (Condition 1) tR=2.47 min, m/z=391.0 [M+H]+, m/z=389.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 4.02 (s, 3H) 7.40 (d, J=8.3 Hz, 2H) 7.88 (d, J=9.3 Hz, 2H) 8.48 (d, J=2.4 Hz, 1H) 8.86 (d, J=2.4 Hz, 1H) 9.13 (s, 2H) 9.23 (s, 1H) 10.47 (s, 1H).

Workup

  1. customthe combined filtrates were evaporated to dryness under reduced pressure
  2. customThe residue was purified by flash chromatography (RediSep® Silica gel column, 4 g, DCM/MeOH+1% NH4OH from 1% to 10% MeOH+1% NH4OH) and preparative HPLC (Condition 8, 30% for 0.2 min

Sources & evidence

ORD record
ord-099c8b849f9b4cd4a2b4c4ceee2dbb14
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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