Cesium carbonate → (Rac)-cis-(1h-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone

HRID 2191964Notes

Reaction equation

HRID 2191964 reaction equation
F[C:2]1[C:3]([C@@H:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([OH:14])[CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[C:24]([C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1)=[O:25].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1>[NH:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[C:24]([C:26]1[CH:31]=[CH:30][C:29]([O:32][C:2]2[C:3]([C@H:8]3[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:28][CH:27]=1)=[O:25]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 59326874(1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanoneHCID 66986535(Rac)-cis-3-(3-fluoropyrazin-2-yl)cyclohexanol

Product 1

HCID 59351182(Rac)-cis-(1h-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of (rac)-cis-3-(3-fluoropyrazin-2-yl)cyclohexanol (140 mg, 0.713 mmol), (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (340 mg, 1.427 mmol), and cesium carbonate (465 mg, 1.427 mmol) in NMP (1.8 ml) was heated in a Biotage™ microwave reactor at 180° C. for 45 min. The mixture was partitioned between H2O(10 ml) and CH2Cl2 (20 ml), the layers were separated, and the aqueous layer was extracted with CH2Cl2 (3×20 ml). The combined organic layers were dried (MgSO4), concentrated under reduced pressure, and the resulting brown oil was purified by reversed phase HPLC (Gilson Gemini-NX 10u C18 110A, 100×50.0 mm, 10% to 95% H2O/MeCN, 0.1% TFA). The product containing fractions were combined, neutralized by the addition of solid Na2CO3, and extracted with CH2Cl2 (3×20 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to deliver (rac)-cis-(1H-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone as a brown foam. MS (ESI, pos. ion) m/z: 415.0 (M+1). IC50 (uM) +++++.

Workup

  1. customThe mixture was partitioned between H2O(10 ml) and CH2Cl2 (20 ml)
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with CH2Cl2 (3×20 ml)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customthe resulting brown oil was purified by reversed phase HPLC (Gilson Gemini-NX 10u C18 110A, 100×50.0 mm, 10% to 95% H2O/MeCN, 0.1% TFA)
  7. additionThe product containing fractions
  8. additionneutralized by the addition of solid Na2CO3
  9. extractionextracted with CH2Cl2 (3×20 mL)
  10. dry with materialThe combined organic layers were dried (MgSO4)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4a4131f9fc5f4792b5b188680569ed00
Source dataset
uspto-grants-2012_12
Patent number
US08329700B2

Reaction notes

Loading…