Sodium Carbonate → 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide

HRID 629120Notes

Reaction equation

HRID 629120 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]([Cl: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+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].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]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 867026266-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide

Product 1

HCID 899064746-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

6-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide (Stage 76.1, 8 g, 17.43 mmol), pyrimidine-5-boronic acid (4.55 g, 34.9 mmol), PdCl2(dppf) (0.638 g, 0.871 mmol), Na2CO3 (26.1 mL of 2 M, 52.3 mmol), and DME (110 mL) were added to a vial, which was sealed, evacuated/purged with argon and the RM was stirred at 90° C. for 20 h. The RM was dissolved in EtOAc (200 mL), washed with water, dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The residue was purified by flash chromatography (Silica gel column, 750 g, EtOAc/n-hexane 1:1) and recrystallized from EtOAc/iPr2O to give the title product as a pink solid. UPLC-MS (Condition 2) tR=1.05 min, m/z=409.0/411.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.38 (d, J=8.60 Hz, 2H) 7.86 (d, J=8.99 Hz, 2H) 8.54 (d, J=1.95 Hz, 1H) 9.01 (br.s., 1H) 9.08 (s, 2H) 9.30 (s, 1H) 10.67 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. dissolutionThe RM was dissolved in EtOAc (200 mL)
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated off under reduced pressure
  7. customThe residue was purified by flash chromatography (Silica gel column, 750 g, EtOAc/n-hexane 1:1)
  8. customrecrystallized from EtOAc/iPr2O

Sources & evidence

ORD record
ord-020befc8119040cb8d0efb2321be0213
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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