Triethylamine → HCID 68645726, compound

HRID 1161357Notes

Reaction equation

HRID 1161357 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:14](O)=[O:15])[C:11]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:35][C:36]1[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)[C:14]([NH:35][C:36]3[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=3)=[O:15])[C:11]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=3[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 133964-AminobenzonitrileHCID 65578Oxalyl chlorideHCID 66619321[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid

Product 1

HCID 68645726HCID 68645726, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To the suspension of 0.5 g (1.24 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid (Ex. 22, int. c) in 3 ml dichloromethane 0.01 ml (0.12 mmol) N,N-dimethylformamide, 0.13 ml (1.54 mmol) oxalylchloride were added dropwise under gas evolution. The resulting clear, light yellow solution was stirred for 1 h at room temperature, then evaporated to dryness, treated twice with 5 ml of dichloromethane and again evaporated to dryness. The light yellow solid was dissolved in 8 ml of dichloromethane and added dropwise to a stirred mixture of 0.13 g (1.24 mmol) 4-aminobenzonitrile and 0.46 ml (3.31 mmol) triethylamine in dichloromethane. After stirring for 3.75 h the clear yellow solution was poured on water and extracted twice with dichloromethane. The organic layers were washed with water and brine, dried over magnesium sulfate, filtered and after addition of silica gel evaporated to dryness. Purification by silica gel column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane to heptan/ethyl acetate (1:0 to 1:1 v/v) yielded 0.45 g (81%) of the title compound as a light brown solid. MS (ES−): M−H: 571.2.

Workup

  1. additionwere added dropwise under gas evolution
  2. customevaporated to dryness
  3. additiontreated twice with 5 ml of dichloromethane
  4. customagain evaporated to dryness
  5. dissolutionThe light yellow solid was dissolved in 8 ml of dichloromethane
  6. stirringAfter stirring for 3.75 h the clear yellow solution
  7. additionwas poured on water
  8. extractionextracted twice with dichloromethane
  9. washThe organic layers were washed with water and brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. additionafter addition of silica gel
  13. customevaporated to dryness
  14. customPurification by silica gel column chromatography
  15. washeluting with a gradient of heptane to heptan/ethyl acetate (1:0 to 1:1 v/v)

Sources & evidence

ORD record
ord-afc3d12c6c10406cb4704e52b970bc31
Source dataset
uspto-grants-2010_10
Patent number
US07816540B2

Reaction notes

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