Sodium Carbonate → HCID 89907349, compound

HRID 923853Notes

Reaction equation

HRID 923853 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].[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1.[C:32]([O-:35])([O-])=O.[Na+].[Na+]>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>[OH:35][C@@H:32]1[CH2:2][CH2:3][N:4]([C:3]2[C:2]([C:27]3[CH:28]=[N:23][CH:24]=[N:25][CH:26]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:5]1

Participants

5

Reactant 3

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

Product 1

HCID 89907349HCID 89907349, compound

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 35.1, 2 g, 4.48 mmol), pyrimidin-5-ylboronic acid (0.666 g, 5.38 mmol), Pd(PPh3)2Cl2 (0.315 g, 0.448 mmol) and Na2CO3 (1.425 g, 13.45 mmol) were added to a MW vial. The vial was sealed, evacuated/purged with argon, and DME (12.55 mL), water (3.59 mL), EtOH (1.793 mL) were added. The RM was stirred at 80° C. for 3.5 h, diluted with THF (4 mL), treated with Si-Thiol (Silicycle, 1.27 mmol/g, 1.765 g, 2.241 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 120 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1), from 60% to 90% EtOAc-EtOH+0.1% NH4OH (9:1)). Crystallization from a toluene/EtOH mixture yielded the title compound as a white amorphous solid. HPLC Chiral (CHIRALPAK® AD-H, 250×4.6 mm, eluent: EtOH, 0.5 mL/min, UV 210 nm) tR=18.58 min, UPLC-MS (condition 1) tR=2.07 min, m/z=446.1 [M+H]+, m/z=444.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.70-1.80 (m, 1H) 1.81-1.92 (m, 1H) 2.89 (d, J=11.25 Hz, 1H) 3.18-3.28 (m, 2H) 3.35-3.44 (m, 1H) 4.22 (br. s, br. s, 1H) 4.89 (d, J=3.42 Hz, 1H) 7.35 (d, J=9.05 Hz, 2H) 7.85 (d, J=9.05 Hz, 2H) 8.10 (d, J=2.45 Hz, 1H) 8.80 (d, J=2.20 Hz, 1H) 8.89 (s, 2H) 9.20 (s, 1H) 10.17 (s, 1H).

Workup

  1. customThe vial was sealed
  2. customevacuated/purged with argon, and DME (12.55 mL), water (3.59 mL), EtOH (1.793 mL)
  3. additionwere added
  4. additiondiluted with THF (4 mL)
  5. filtrationfiltered
  6. customthe filtrate was evaporated off under reduced pressure
  7. customto give a residue which
  8. customwas purified by flash chromatography (RediSep® Silica gel column, 120 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1), from 60% to 90% EtOAc-EtOH+0.1% NH4OH (9:1))
  9. customCrystallization from a toluene/EtOH mixture

Sources & evidence

ORD record
ord-613ef5ce509444e185fd19aa5dfdcf83
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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