Potassium Phosphate, Tribasic → HCID 118195148, compound

HRID 923874Notes

Reaction equation

HRID 923874 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]2)=[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].[CH3:28][O:29][C:30]1[N:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:27][C@@H:24]1[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:33]3[CH:34]=[N:35][C:30]([O:29][CH3:28])=[CH:31][CH:32]=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)[CH2:23]1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 86702593(R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 118195148HCID 118195148, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

(R)-5-Bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 35.1, 60 mg, 0.134 mmol), (6-methoxypyridin-3-yl)boronic acid (25.2 mg, 0.161 mmol), Pd2(dba)3 (2.463 mg, 2.69 μmol), 2-diclyclohexylphosphino-2′,4′,6′-triisoprophylbiphenyl (2.56 mg, 5.38 μmol) and K3PO4 (86 mg, 0.403 mmol) were added to a MW vial. The vial was sealed, evacuated/purged with argon, and BuOH (269 μL) was added. The RM was stirred at 100° C. for 16 h, diluted with THF (1 mL), treated with Si-Thiol (Silicycle, 1.27 mmol/g, 52.9 mg, 0.067 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 12, from 30% to 60% in 12 min.) to afford the title compound as a white solid. UPLC-MS (condition 1) tR=2.36 min, m/z=475.2 [M+H]+, m/z=473.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.78 (m, 1H) 1.77-1.90 (m, 1H) 2.93 (d, J=11.74 Hz, 1H) 3.18-3.26 (m, 2H) 3.35-3.46 (m, 1H) 3.91 (s, 3H) 4.20 (br. s, 1H) 4.83 (d, J=3.42 Hz, 1H) 6.91 (d, J=8.56 Hz, 1H) 7.34 (d, J=8.56 Hz, 2H) 7.72 (dd, J=8.56, 2.45 Hz, 1H) 7.86 (d, J=9.05 Hz, 2H) 7.97 (d, J=2.20 Hz, 1H) 8.21 (d, J=2.45 Hz, 1H) 8.74 (d, J=2.20 Hz, 1H) 10.14 (s, 1H).

Workup

  1. customThe vial was sealed
  2. customevacuated/purged with argon, and BuOH (269 μL)
  3. additionwas added
  4. additiondiluted with THF (1 mL)
  5. filtrationfiltered
  6. customthe filtrate was evaporated off under reduced pressure
  7. customto give a residue which
  8. customwas purified by preparative HPLC (Condition 12, from 30% to 60% in 12 min.)

Sources & evidence

ORD record
ord-c842d96cb02e467fbe64b88275878cc7
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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