1,2-Dichloroethane → N-[(1R)-1-(5-Fluoro-1-oxidopyridin-2-yl)ethyl]-3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzamide

HRID 1257546Notes

Reaction equation

HRID 1257546 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]([CH:14]=[C:15]([C:17]3[CH2:21][C@@H:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[O:19][N:18]=3)[CH:16]=2)[C:11](O)=[O:12])=[N:6][CH:7]=1.Cl.[F:29][C:30]1[CH:31]=[CH:32][C:33]([C@H:37]([NH2:39])[CH3:38])=[N+:34]([O-:36])[CH:35]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C)C=O>[F:29][C:30]1[CH:31]=[CH:32][C:33]([C@H:37]([NH:39][C:11](=[O:12])[C:10]2[CH:14]=[C:15]([C:17]3[CH2:21][C@@H:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[O:19][N:18]=3)[CH:16]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)[CH:9]=2)[CH3:38])=[N+:34]([O-:36])[CH:35]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 66894903HCID 66894903, compoundHCID 66895339(1R)-1-(5-fluoro-1-oxidopyridin-2-yl)ethanamine hydrochloride salt

Product 1

HCID 42634194N-[(1R)-1-(5-Fluoro-1-oxidopyridin-2-yl)ethyl]-3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzamideYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoic acid (50.0 mg, 0.12 mmol) in N,N-dimethylformamide (1 mL) were added (1R)-1-(5-fluoro-1-oxidopyridin-2-yl)ethanamine hydrochloride salt (33.4 mg, 0.17 mmol), EDC (33.3 mg, 0.17 mmol), HOAT (7.9 mg, 0.06 mmol) and triethylamine (0.11 mL, 0.81 mmol). The reaction mixture was stirred at ambient temperature for 1.5 h. The reaction mixture was heated to 50° C. After 20 min, the mixture was cooled to ambient temperature and the solid in the reaction was filtered off. Purification by reverse phase chromatography (C-18, 95% water/acetonitrile→65% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (46 mg). HRMS 498.1954 (M+1). 1H NMR (400 MHz, CDCl3): δ 8.56 (d, J=4.8 Hz, 1H); 8.48 (s, 1H); 8.46-8.35 (m, 3H); 8.15-8.08 (m, 2H); 7.73-7.65 (m, 2H); 7.54 (t, J=8.9 Hz, 2H); 7.34 (t, J=7.8 Hz, 1H); 7.20 (dd, J=7.7, 4.8 Hz, 1H); 7.06 (ddd, J=8.8, 6.6, 2.4 Hz, 1H); 5.86 (dd, J=10.9, 6.9 Hz, 1H); 5.58-5.48 (m, 1H); 3.92-3.74 (m, 2H); 2.35 (s, 3H); 1.70 (d, J=7.0 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was heated to 50° C
  2. waitAfter 20 min
  3. temperaturethe mixture was cooled to ambient temperature
  4. filtrationthe solid in the reaction was filtered off
  5. customPurification by reverse phase chromatography (C-18, 95% water/acetonitrile→65% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-bd098c8a8de348a79dc52185bea56691
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

Loading…