Sodium Carbonate → (R)-5-(2-Aminopyrimidin-5-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 923855Notes

Reaction equation

HRID 923855 reaction equation
Cl[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].[NH2:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[NH2:28][C:29]1[N:34]=[CH:33][C:32]([C:2]2[C:3]([N:22]3[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]3)=[N:4][CH:5]=[C:6]([CH:21]=2)[C:7]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][C:17]([F:18])([F:19])[F:20])=[CH:14][CH:15]=2)=[O:8])=[CH:31][N:30]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 17750211(2-Aminopyrimidin-5-yl)boronic acidHCID 89907107(R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 118195268(R)-5-(2-Aminopyrimidin-5-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of (R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 38.1, 50 mg, 0.124 mmol), (2-aminopyrimidin-5-yl)boronic acid (26 mg, 0.187 mmol), 2 M Na2CO3 (0.124 mL, 0.249 mmol) and DME (2.5 mL) was flushed with argon and PdCl2(dppf)(CH2Cl2) (10 mg, 0.012 mmol) was added. The mixture was subjected to MW irradiation 140° C. for 30 min, passed through a PL-Thiol MP SPE cartridge (StratoSpheres™), the cartridge was washed with MeOH and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative LC-MS to afford the title compound. LC-MS (Condition 5) tR=1.53 min, m/z=461.1 [M+H]+, m/z=459.1 [M−H]−.

Workup

  1. additionwas added
  2. customThe mixture was subjected to MW irradiation 140° C. for 30 min
  3. washthe cartridge was washed with MeOH
  4. customthe solvent was evaporated off under reduced pressure
  5. customto give a residue which
  6. customwas purified by preparative LC-MS

Sources & evidence

ORD record
ord-df9295a0209d4682bb6ef9521b5bb61b
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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