Toluene → 6-(2-Methoxyethoxy)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 629088Notes

Reaction equation

HRID 629088 reaction equation
Br[C:2]1[C:3]([O:22][CH2:23][CH2:24][O:25][CH3:26])=[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].CC1(C)C(C)(C)OB([C:35]2[CH:36]=[N:37][CH:38]=[N:39][CH:40]=2)O1.C1(C)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:26][O:25][CH2:24][CH2:23][O:22][C:3]1[C:2]([C:35]2[CH:36]=[N:37][CH:38]=[N:39][CH:40]=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

7

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 4192667Pyrimidine-5-boronic acid, pinacol esterHCID 899074165-bromo-6-(2-methoxyethoxy)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 722020096-(2-Methoxyethoxy)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

A mixture of 5-bromo-6-(2-methoxyethoxy)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 51.1, 50 mg, 0.115 mmol) Pd(Ph3P)4 (13 mg, 0.011 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (36 mg, 0.172 mmol) and toluene (0.5 mL) was stirred for 15 min. at RT. K3PO4 (73 mg, 0.345 mmol) was added and the RM was stirred at 110° C. for 6 h. The RM was diluted with MeOH, filtered through a cartridge of PL-Thiol MP-Resin, and the filtrate was evaporated to dryness under reduced pressure. The residue was purified by preparative SFC (Column DEAP, from 7% to 12% in 6 min) to afford the title compound was lyophilized to afford an off-white powder. UPLC-MS (Condition 2) tR=1.04 min, m/z=435.1 [M+H]+.

Workup

  1. stirringthe RM was stirred at 110° C. for 6 h
  2. filtrationfiltered through a cartridge of PL-Thiol MP-Resin
  3. customthe filtrate was evaporated to dryness under reduced pressure
  4. customThe residue was purified by preparative SFC (Column DEAP, from 7% to 12% in 6 min)

Sources & evidence

ORD record
ord-614d217b084748d1a8de7cb046cf9d9d
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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