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

HRID 525653Notes

Reaction equation

HRID 525653 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].CC1(C)C(C)(C)OB([C:36]2[CH:37]=[C:38]([CH2:41][OH:42])[S:39][CH:40]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[OH:42][CH2:41][C:38]1[S:39][CH:40]=[C:36]([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:15]=[CH:14][C:13]([O:16][C:17]([F:18])([F:20])[F:19])=[CH:12][CH:11]=2)=[O:8])[CH:37]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 17749899(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)methanolHCID 89907107(R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 118044930(R)-5-(5-(Hydroxymethyl)thiophen-3-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.1, 50 mg, 0.124 mmol), (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)methanol (45 mg, 0.187 mmol), 2 M Na2CO3 (0.124 mL, 0.249 mmol) and DME (2.5 mL) were added to a MW vial, which was sealed and evacuated/purged with argon. PdCl2(dppf)-(CH2Cl2) was added (10 mg, 0.012 mmol) and the mixture was stirred at 140° C. for 30 min. The RM was filtered 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 1.55 min, m/z=479.9 [M+H]+.

Workup

  1. additionwere added to a MW vial, which
  2. customwas sealed
  3. customevacuated/purged with argon
  4. additionPdCl2(dppf)-(CH2Cl2) was added (10 mg, 0.012 mmol)
  5. filtrationThe RM was filtered through a PL-Thiol MP SPE cartridge (StratoSpheres™)
  6. washthe cartridge was washed with MeOH
  7. customthe solvent was evaporated off under reduced pressure
  8. customto give a residue which
  9. customwas purified by preparative LC-MS

Sources & evidence

ORD record
ord-fbba59f454ad4a568476f0e53b66e980
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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