Cesium carbonate → (1H-Benzo[D]imidazol-2-YL)(4-(3-(4-fluorotetrahydro-2H-pyran-4-YL)pyrazin-2-yloxy)phenyl)methanone

HRID 2191985Notes

Reaction equation

HRID 2191985 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)=[O:11].F[C:20]1[C:25]([C:26]2([F:32])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[N:24][CH:23]=[CH:22][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:20]2[C:25]([C:26]3([F:32])[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)=[N:24][CH:23]=[CH:22][N:21]=2)=[CH:14][CH:13]=1)=[O:11]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 59326874(1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanoneHCID 593511352-Fluoro-3-(4-fluorotetrahydro-2H-pyran-4-YL)pyrazine

Product 1

HCID 59351177(1H-Benzo[D]imidazol-2-YL)(4-(3-(4-fluorotetrahydro-2H-pyran-4-YL)pyrazin-2-yloxy)phenyl)methanone

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (0.543 g, 2.278 mmol),2-fluoro-3-(4-fluorotetrahydro-2H-pyran-4-yl)pyrazine (0.304 g, 1.519 mmol), cesium carbonate (0.990 g, 3.04 mmol), and N-Methyl-2-pyrrolidinone (3.04 mL) in a sealed tube was heated to 100° C. overnight. Aqueous work up with DCM and washing with alternating water and brine washes. The organic layer was rotovapped and loaded onto a Biotage samplet. Purification by Biotage (0-100% EtOAc/hexane, slow gradient, over 12 CV). The product containing fractions were concentrated by rotovap. The residue was further purified by trituration with EtOH at room temperature overnight to produce product. MS (ESI, pos. ion) m/z: 419.1 (M+1). IC50 (uM) +++++.

Workup

  1. washAqueous work up with DCM and washing with alternating water and brine washes
  2. customPurification by Biotage (0-100% EtOAc/hexane, slow gradient, over 12 CV)
  3. additionThe product containing fractions
  4. concentrationwere concentrated by rotovap
  5. customThe residue was further purified by trituration with EtOH at room temperature overnight
  6. customto produce product

Sources & evidence

ORD record
ord-5a4b1ae32cb7463d913e13efed616953
Source dataset
uspto-grants-2012_12
Patent number
US08329700B2

Reaction notes

Loading…