Sodium Carbonate → 6-Chloro-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 629095Notes

Reaction equation

HRID 629095 reaction equation
[Cl:1][C:2]1[C:21](I)=[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][N:3]=1.[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[Cl:1][C:2]1[C:21]([C:27]2[CH:28]=[N:23][CH:24]=[N:25][CH:26]=2)=[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][N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 867025996-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 722034246-Chloro-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 56.1, 5.7 g, 12.75 mmol), pyrimidine-5-boronic acid (2.5 g, 19.77 mmol), PdCl2(dppf)-(CH2Cl2) (0.625 g, 0.765 mmol), Na2CO3 (19.13 mL, 38.3 mmol) and DME (100 mL) was stirred at 80° C. for 2.5 h under argon atmosphere. The RM was filtered through Hyflo®, diluted with EtOAc (100 mL), washed with a sat. aq. solution of NaHCO3 and with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Biotage Silica gel column, 120 g, Eluent: n-hexane/EtOAc from 20% to 60% EtOAc) to give the title compound product as a pink crystalline solid. UPLC-MS (Condition 2) tR=1.01 min, 393.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.42 (d, J=8.99 Hz, 2H) 7.88 (d, J=9.38 Hz, 2H) 8.56 (d, J=2.35 Hz, 1H) 9.03 (d, J=2.35 Hz, 1H) 9.10 (s, 2H) 9.32 (s, 1H) 10.69 (s, 1H).

Workup

  1. filtrationThe RM was filtered through Hyflo®
  2. additiondiluted with EtOAc (100 mL)
  3. washwashed with a sat. aq. solution of NaHCO3 and with brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give the crude product which
  7. customwas purified by flash chromatography (Biotage Silica gel column, 120 g, Eluent: n-hexane/EtOAc from 20% to 60% EtOAc)

Sources & evidence

ORD record
ord-f8da881e6ade485193787a0cb89cd8f3
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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