Ethylene Glycol → HCID 72202876, compound

HRID 629050Notes

Reaction equation

HRID 629050 reaction equation
[H-].[Na+].[CH2:3]([OH:6])[CH2:4][OH:5].Cl[C:8]1[N:13]=[CH:12][C:11]([C:14]2[CH:15]=[C:16]([CH:31]=[CH:32][CH:33]=2)[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=2)=[O:18])=[CH:10][N:9]=1>C1COCC1>[OH:5][CH2:4][CH2:3][O:6][C:8]1[N:9]=[CH:10][C:11]([C:14]2[CH:15]=[C:16]([CH:31]=[CH:32][CH:33]=2)[C:17]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([O:26][C:27]([F:30])([F:28])[F:29])=[CH:24][CH:25]=2)=[O:18])=[CH:12][N:13]=1

Participants

5

Reactant 3

HCID 174Ethylene Glycol2×HCID 24758Sodium hydrideHCID 89907216HCID 89907216, compound

Product 1

HCID 72202876HCID 72202876, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH 60% in oil (12.19 mg, 0.508 mmol) in THF (200 μL) was added ethylene glycol (21.24 μL, 0.381 mmol). A solution of 3-(2-chloropyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 2.1, 50 mg, 0.127 mmol) in THF (2.5 mL) was then added and the RM was stirred at RT overnight. Additional ethylene glycol (200 μL, 3.59 mmol) was added and the reaction was stirred at RT for 4 h. The reaction was quenched with HCOOH and the solvent was evaporated off under reduced pressure. The residue was treated with saturated aq. NaHCO3 (10 mL) and extracted with TBME/EtOAc (1:1). The combined extracts were washed with brine, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 4 g, DCM/MeOH+1% NH4OH, from 1% to 12% MeOH+1% NH4OH) to afford the title compound as a white solid. UPLC-MS (Condition 1) tR=2.44 min, m/z=420.1 [M+H]+, m/z=418.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.76 (dd, 2H) 4.40 (t, 2H) 4.92 (t, J=5.5 Hz, 1H) 7.39 (d, J=8.6 Hz, 2H) 7.64-7.70 (m, 1H) 7.91 (d, J=9.0 Hz, 2H) 7.97 (d, J=8.1 Hz, 2H) 8.28 (s, 1H) 9.04 (s, 2H) 10.48 (s, 1H).

Workup

  1. stirringthe reaction was stirred at RT for 4 h
  2. customThe reaction was quenched with HCOOH
  3. customthe solvent was evaporated off under reduced pressure
  4. additionThe residue was treated with saturated aq. NaHCO3 (10 mL)
  5. extractionextracted with TBME/EtOAc (1:1)
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. customthe solvent was evaporated off under reduced pressure
  9. customto give the crude product which
  10. customwas purified by flash chromatography (Silica gel column, 4 g, DCM/MeOH+1% NH4OH, from 1% to 12% MeOH+1% NH4OH)

Sources & evidence

ORD record
ord-ec3393f724934f4285b60de718f3ef9a
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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