Acetic Acid → HCID 178433274, compound

HRID 1365522Notes

Reaction equation

HRID 1365522 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([F:27])[CH:18]=2)([NH2:16])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.[CH3:28][C:29]1[N:30]=[CH:31][NH:32][C:33]=1[CH:34]=O.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:24])[F:25])[CH:20]=[C:19]([F:27])[CH:18]=2)([NH:16][CH2:34][C:33]2[NH:32][CH:31]=[N:30][C:29]=2[CH3:28])[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 27958875-Methyl-1H-imidazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 591345731-(5-Chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine

Product 1

HCID 178433274HCID 178433274, compoundYield 93.8%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine (0.02 g, 0.051 mmol) in dichloroethane (0.5 mL) in a two dram vial was added 4-methyl-1H-imidazole-5-carbaldehyde (6 mg, 0.051 mmol), followed by a drop of acetic acid. The reaction mixture was shaken for 20 minutes at room temperature and then NaBH(OAc)3 was added (12 mg, 0.056 mmol). The reaction was stirred at room temperature overnight. The solvents were removed and the residue was purified by preparative HPLC (phenominex C18 column, 21×100 mm, 5μ) using MeOH/H2O (with 0.1% TFA) to give 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-N-((4-methyl-1H-imidazol-5-yl)methyl)-2-phenylethanamine as a white solid (23.4 mg, 76% yield). LCMS: 3.6 min [M+1] 489.2 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 2.27 (s, 3 H), 3.45-3.52 (m, 1 H), 3.88-3.99 (m, 2 H), 4.01-4.07 (m, 1 H), 6.64 (d, J=7.09 Hz, 2 H), 7.02 (d, J=8.56 Hz, 1 H), 7.10 (t, J=7.46 Hz, 2 H), 7.18 (t, J=7.46 Hz, 1 H), 7.49 (d, J=7.58 Hz, 1 H), 7.61 (d, J=9.54 Hz, 1 H), 7.69 (s, 1 H), 7.76 (dd, J=8.56, 2.45 Hz, 1 H), 8.28 (s, 1 H), 8.60 (d, J=1.96 Hz, 1 H).

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. customThe solvents were removed
  3. customthe residue was purified by preparative HPLC (phenominex C18 column, 21×100 mm, 5μ)

Sources & evidence

ORD record
ord-2fa69137c6b14fa0bb181e50dffac910
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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