1,2-Dichloroethane → 3-(3-fluoropyridin-2-yl)-N-[(1R)-1-(5-fluoropyridin-2-yl)ethyl]-5-(5-methylpyridin-2-yl)benzamide

HRID 888394Notes

Reaction equation

HRID 888394 reaction equation
[Cl-].[Na+].[F:3][C:4]1[C:5]([C:10]2[CH:11]=[C:12]([CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=3)[CH:18]=2)[C:13]([OH:15])=O)=[N:6][CH:7]=[CH:8][CH:9]=1.Cl.[F:27][C:28]1[CH:29]=[CH:30][C:31]([C@H:34]([NH2:36])[CH3:35])=[N:32][CH:33]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C)C=O>[F:3][C:4]1[C:5]([C:10]2[CH:11]=[C:12]([CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=3)[CH:18]=2)[C:13]([NH:36][C@@H:34]([C:31]2[CH:30]=[CH:29][C:28]([F:27])=[CH:33][N:32]=2)[CH3:35])=[O:15])=[N:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 5234Sodium ChlorideHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 66690953(R)-1-(5-Fluoropyridin-2-yl)ethanamine hydrochlorideHCID 68496637HCID 68496637, compound

Product 1

HCID 252567493-(3-fluoropyridin-2-yl)-N-[(1R)-1-(5-fluoropyridin-2-yl)ethyl]-5-(5-methylpyridin-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the sodium chloride salt of 3-(3-fluoropyridin-2-yl)-5-(5-methylpyridin-2-yl)benzoic acid (25.0 mg, 0.05 mmol) in N,N-dimethylformamide (0.35 mL) were added (1R)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride salt (16.5 mg, 0.08 mmol), EDC (14.9 mg, 0.08 mmol), HOBT (7.92 mg, 0.05 mmol) and triethylamine (21.6 μL, 0.16 mmol). The reaction mixture was stirred at ambient temperature. After 18 h, the mixture was cooled to ambient temperature. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→50% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound. HRMS 431.1706 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.73 (q, J=1.6 Hz, 1H); 8.57-8.54 (m, 2H); 8.52 (t, J=1.7 Hz, 1H); 8.45 (q, J=1.5 Hz, 1H); 8.44 (d, J=2.8 Hz, 1H); 7.78 (d, J=8.1 Hz, 1H); 7.62-7.52 (m, 3H); 7.43-7.31 (m, 3H); 5.43 (p, J=7.0 Hz, 1H); 2.40 (s, 3H); 1.61 (d, J=6.8 Hz, 3H).

Workup

  1. temperaturethe mixture was cooled to ambient temperature
  2. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→50% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-65f3273bed1647e9938f50ca54aad221
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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