1,2-Dimethoxyethane → HCID 178522238, compound

HRID 73729Notes

Reaction equation

HRID 73729 reaction equation
COCCOC.Br[C:8]1[C:9]([N:28]2[CH2:32][CH2:31][C@@H:30]([OH:33])[CH2:29]2)=[N:10][CH:11]=[C:12]([CH:27]=1)[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=1)=[O:14].[NH:34]1[CH:38]=[CH:37][C:36](B(O)O)=[N:35]1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CCO.O>[OH:33][C@@H:30]1[CH2:31][CH2:32][N:28]([C:9]2[C:8]([C:38]3[CH:37]=[CH:36][NH:35][N:34]=3)=[CH:27][C:12]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)=[O:14])=[CH:11][N:10]=2)[CH2:29]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 86702593(R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamideHCID 178514837HCID 178514837, compound2×

Product 1

HCID 178522238HCID 178522238, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of DME (570 μL), water (163 μL) and EtOH (81 μL) was added to a mixture of (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 2.2, 60 mg, 0.134 mmol), (1H-pyrazol-3-yl)boronic acid (45.1 mg, 0.403 mmol) Pd(PPh3)2Cl2 (9.44 mg, 0.013 mmol), Na2CO3 (42.8 mg, 0.403 mmol) in a MW vial. The vial was sealed, evacuated/purged 3 times with argon and the RM was subjected to MW irradiation at 120° C. for 10 min. Additional (1H-pyrazol-3-yl)boronic acid (45.1 mg, 0.403 mmol) was added and the RM was subjected to MW irradiation at 120° C. for 30 min, diluted with THF (1 mL) and 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 9, 15% for 0.2 min then 15% to 45% in 14 min) to yield the title compound as a white solid.

Workup

  1. customThe vial was sealed
  2. customevacuated/purged 3 times with argon
  3. customthe RM was subjected to MW irradiation at 120° C. for 10 min
  4. customthe RM was subjected to MW irradiation at 120° C. for 30 min
  5. filtrationfiltered
  6. customthe filtrate was evaporated off under reduced pressure
  7. customto give a residue which
  8. customwas purified by preparative HPLC (Condition 9, 15% for 0.2 min

Sources & evidence

ORD record
ord-1fd5dbf5bb3142b383bd5e717d5f7624
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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