Methyl 1-[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate → HCID 178467365, compound

HRID 567402Notes

Reaction equation

HRID 567402 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:20]3[C:21]([C:25]([O:27][CH3:28])=[O:26])=[CH:22][CH:23]=[CH:24][C:19]=3[N:18]=[C:17]2[O:29][CH2:30][CH3:31])=[CH:11][CH:10]=1)#[N:2].C([Sn]([N:57]=[N+:58]=[N-:59])(CCCCCCCC)CCCCCCCC)CCCCCCC>C1(C)C=CC=CC=1>[CH2:30]([O:29][C:17]1[N:16]([CH2:15][C:12]2[CH:11]=[CH:10][C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[C:1]3[NH:59][N:58]=[N:57][N:2]=3)=[CH:14][CH:13]=2)[C:20]2[C:21]([C:25]([O:27][CH3:28])=[O:26])=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=1)[CH3:31]

Participants

4

Reactant 2

HCID 15654674Methyl 1-[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-2-ethoxy-1H-benzimidazole-7-carboxylateHCID 713541223-(Trioctylstannyl)triaza-1,2-dien-2-ium-1-ide

Product 1

HCID 178467365HCID 178467365, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
117.5 °C

Procedure

A mixture of methyl 1-[(2′-cyanobiphenyl-4-yl)-methyl]-2-ethoxybenzimidazole-7-carboxylate [BEC] (228 kg) obtained in Reference Example 5, the residue containing trioctyltin azide [TOTA] obtained in Reference Example 6 and toluene (1148 L) was heated for about 40 hours under reflux (115-120° C.). The reaction solution was cooled and concentrated under reduced pressure. To the residue were added ethanol (764 kg) and sodium nitrite solution (135 kg/460 L) and the solution was adjusted to pH 4.5-5.5 with concentrated hydrochloric acid (about 224 kg). To the solution was added ethyl acetate (735 L) and the solution was adjusted to pH 0.5-1.5 with concentrated hydrochloric acid (about 100 L). To the solution was added hexane (1005 L) and the solution was adjusted to pH 3.5±0.5 with 4% sodium hydroxide solution. The solution was cooled to 10° C. or less and stirred for 1 hour. The crystals were separated and washed with a mixture of ethyl acetate (106 L) and hexane (310 L), followed by hexane (410 L) to give wet MET (396.6 kg).

Workup

  1. customobtained in Reference Example 5
  2. temperaturewas heated for about 40 hours
  3. temperatureThe reaction solution was cooled
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue were added ethanol (764 kg) and sodium nitrite solution (135 kg/460 L)
  6. additionTo the solution was added ethyl acetate (735 L)
  7. additionTo the solution was added hexane (1005 L)
  8. temperatureThe solution was cooled to 10° C. or less
  9. customThe crystals were separated
  10. washwashed with a mixture of ethyl acetate (106 L) and hexane (310 L)
  11. customto give wet MET (396.6 kg)

Sources & evidence

ORD record
ord-c086af35d8e1486481edc9f4f5b67f6e
Source dataset
uspto-grants-2001_01
Patent number
US06177587B1

Reaction notes

Loading…