HCID 53741197, compound → HCID 44383311, compound

HRID 1432945Notes

Reaction equation

HRID 1432945 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=4)[C:13](=[O:26])[CH2:12]3)[NH:7][C:6]=2[CH:27]=1.C(OC([N:38]1CCN(CC2C=CC(C#N)=CC=2)C(=O)C1)=O)C1C=CC=CC=1.ClC1C=CC2NC(CCl)=NC=2C=1>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]4[CH:25]=[CH:24][C:21]([C:22]([NH2:38])=[NH:23])=[CH:20][CH:19]=4)[C:13](=[O:26])[CH2:12]3)[NH:7][C:6]=2[CH:27]=1

Participants

5

Reactant 3

HCID 53741197HCID 53741197, compoundHCID 54447690HCID 54447690, compoundHCID 178478447HCID 178478447, compound

Product 1

HCID 44383311HCID 44383311, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Hydrogen chloride gas is bubbled into an ice-cooled solution of 4-[4-(6-chloro-1H-benzoimidazol-2-ylmethyl)-2-oxo-piperazin-1-ylmethyl]-benzonitrile (100 mg, 0.264 mmol), (prepared by deprotecting 4-(4-cyanobenzyl)-3-oxopiperazine-1-carboxylic acid benzyl ester, EXAMPLE 66, Part A, followed by alkylation with 6-chloro-2-chloromethylbenzimidazole) in 15 mL of methanol. The solution contained 3Å molecular sieves. The reaction mixture is stored at −30° C. The methanol is removed on the rotovap. Fresh methanol (20 ml) is added folowed by a stream of ammonia gas. The resulting mixture is heated to reflux for three hours. The reaction mixture is filtered at room temperature. The mother liquor is condensed and the resulting residue is purified by reverse phase HPLC (0-50% ACN/H2O). The product is isolated as a white solid with a melting point of 91-95° C. MS C20H21ClN6O m/z: 397, 399. Anal. cald. for C20H21ClN6O.3C2HF3O2: C, 42.26; H, 3.27; N, 11.37. Found C, 42.20; H, 3.44; N, 11.36.

Workup

  1. customHydrogen chloride gas is bubbled into an ice-
  2. temperaturecooled
  3. customis stored at −30° C
  4. customThe methanol is removed on the rotovap
  5. additionFresh methanol (20 ml) is added
  6. temperatureThe resulting mixture is heated
  7. temperatureto reflux for three hours
  8. filtrationThe reaction mixture is filtered at room temperature
  9. customcondensed
  10. customthe resulting residue is purified by reverse phase HPLC (0-50% ACN/H2O)
  11. customThe product is isolated as a white solid with a melting point of 91-95° C

Sources & evidence

ORD record
ord-7771cce7ad2541a396d94427d494fec0
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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