Acetic Acid → 2-Fluoro-4-(5-{[(3'-hydroxybiphenyl-2-ylmethyl)amino]methyl}imidazol-1-ylmethyl)benzonitrile

HRID 278171Notes

Reaction equation

HRID 278171 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[CH:11]=1.[C:17]([C:19]1[CH:32]=[CH:31][C:22]([CH2:23][N:24]2[C:28]([CH:29]=O)=[CH:27][N:26]=[CH:25]2)=[CH:21][C:20]=1[F:33])#[N:18].[BH3-]C#N.[Na+].CC(O)=O>CO>[F:33][C:20]1[CH:21]=[C:22]([CH2:23][N:24]2[C:28]([CH2:29][NH:2][CH2:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[CH:11]=3)=[CH:27][N:26]=[CH:25]2)[CH:31]=[CH:32][C:19]=1[C:17]#[N:18]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 114247081-(4-Cyano-3-fluorobenzyl)-5-imidazolecarboxaldehydeHCID 226270902-Aminomethyl-3'-hydroxybiphenyl hydrochloride

Product 1

HCID 226271012-Fluoro-4-(5-{[(3'-hydroxybiphenyl-2-ylmethyl)amino]methyl}imidazol-1-ylmethyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-Aminomethyl-3′-hydroxybiphenyl hydrochloride from Step H (129 mg, 0.548 mmol) and 1-(4-cyano-3-fluorobenzyl)-5-imidazolecarboxaldehyde from Example 3, Step G (132 mg, 0.576 mmol) were stirred in MeOH (2 mL) for 30 min, then NaCNBH3 (38 mg, 0.60 mmol) was added. The reaction mixture was adjusted to pH 5 with AcOH, as judged from wetted pH paper, and stirring was continued at ambient temperature for 3 days. The reaction was quenched with 10% aq. citric acid and stirred for 20 min. Sat. aq. NaHCO3 (10 mL) was added and the mixture was extracted with CH2Cl2 (4×20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The titled product was crystallized from CH2Cl2-hexane and the first crop of white needles used for the next reaction.

Workup

  1. customThe reaction was quenched with 10% aq. citric acid
  2. stirringstirred for 20 min
  3. additionSat. aq. NaHCO3 (10 mL) was added
  4. extractionthe mixture was extracted with CH2Cl2 (4×20 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe titled product was crystallized from CH2Cl2-hexane
  9. customthe first crop of white needles used for the next reaction

Sources & evidence

ORD record
ord-791e297a08534f0b81a3500a6d22a808
Source dataset
uspto-grants-2002_03
Patent number
US06358985B1

Reaction notes

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