Ethyl chloroformate → HCID 16071133, compound

HRID 2064214Notes

Reaction equation

HRID 2064214 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[CH2:11][CH2:10]2)[C:5]([NH2:21])=[CH:4][C:3]=1[C:22]([F:25])([F:24])[F:23].C(N(C(C)C)CC)(C)C.Cl[C:36](OCC)=[O:37]>O1CCCC1>[Br:1][C:2]1[C:3]([C:22]([F:23])([F:25])[F:24])=[CH:4][C:5]2[NH:21][C:36](=[O:37])[N:8]([CH:9]3[CH2:10][CH2:11][N:12]([CH:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[CH2:13][CH2:14]3)[C:6]=2[CH:7]=1

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 59850187HCID 59850187, compound

Product 1

HCID 16071133HCID 16071133, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

A stirred solution of 5-bromo-N-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-4-(trifluoromethyl)-1,2-benzenediamine (D55) (0.34 mmol) in tetrahydrofuran (8 ml) at room temperature under argon was treated with diisopropylethylamine (0.12 ml, 0.68 mmol) followed by ethyl chloroformate (40 mg, 0.38 mmol) and then heated under reflux for 2 hrs. The mixture was concentrated under vacuum and the residue dissolved in dimethylformamide, treated with more diisopropylethylamine (0.12 ml) and heated at 150° C. for 0.75 hr. The solution was then concentrated under vacuum and the residue treated with 10% Na2CO3 solution and extracted with ethyl acetate. The extract was dried and concentrated under vacuum. The residue was triturated with diethyl ether to afford 6-bromo-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one as a beige solid. This was converted to its HCl salt as a beige solid (55 mg, 33%). MH+=448, 450.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 2 hrs
  3. concentrationThe mixture was concentrated under vacuum
  4. dissolutionthe residue dissolved in dimethylformamide
  5. additiontreated with more diisopropylethylamine (0.12 ml)
  6. concentrationThe solution was then concentrated under vacuum
  7. additionthe residue treated with 10% Na2CO3 solution
  8. extractionextracted with ethyl acetate
  9. customThe extract was dried
  10. concentrationconcentrated under vacuum
  11. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-564f4788d3694b41bfc6a3bb2b3c0053
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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