Sodium Carbonate → HCID 89908080, compound

HRID 923881Notes

Reaction equation

HRID 923881 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].[CH:28]1[C:37]2[C:32](=[CH:33][CH:34]=[C:35](B(O)O)[CH:36]=2)[CH:31]=[CH:30][N:29]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[OH:27][C@@H:24]1[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:35]3[CH:36]=[C:37]4[C:32]([CH:31]=[CH:30][N:29]=[CH:28]4)=[CH:33][CH:34]=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 10340Sodium CarbonateHCID 23597419Isoquinolin-7-ylboronic acidHCID 86702593(R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 89908080HCID 89908080, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 35.1, 60 mg, 0.134 mmol), isoquinolin-7-ylboronic acid (35 mg, 0.202 mmol), 2 M Na2CO3 (0.134 mL) and DME (4 mL) was flushed with argon. PdCl2(dppf)(CH2Cl2) (11 mg, 0.013 mmol) was added and the mixture was subjected to MW irradiation at 140° C. for 30 min. The RM was filtered through a PL-Thiol MP SPE cartridge (StratoSpheres™, 6 mL), 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 as a beige powder. LC-MS (Condition 6) tR=1.33 min, m/z=495.1 [M+H]+.

Workup

  1. customwas flushed with argon
  2. customthe mixture was subjected to MW irradiation at 140° C. for 30 min
  3. filtrationThe RM was filtered through a PL-Thiol MP SPE cartridge (StratoSpheres™, 6 mL)
  4. washthe cartridge was washed with MeOH
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by preparative LC-MS

Sources & evidence

ORD record
ord-b810243c2cc34645a24b75c838c1b6c4
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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