1,2-Dichloroethane → HCID 66895517, compound

HRID 1257532Notes

Reaction equation

HRID 1257532 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:36]([NH2:38])[CH3:37])=[N:34][CH:35]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C)C=O.O>[F:29][C:30]1[CH:31]=[CH:32][C:33]([C@H:36]([NH:38][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)[CH3:37])=[N:34][CH:35]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 66690953(1R)-1-(5-fluoropyridin-2-yl)ethan-1-amine hydrochlorideHCID 66894903HCID 66894903, compound

Product 1

HCID 66895517HCID 66895517, compoundYield 81.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoic acid (11.7 g, 27.1 mmol) in N,N-dimethylformamide (150 mL) were added (1R)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride salt (7.5 g, 35.2 mmol), EDC (7.78 g, 40.6 mmol), HOAT (1.84 g, 13.5 mmol) and triethylamine (26.4 mL, 189 mmol). The reaction mixture was heated to 50° C. After 2 h, the mixture was cooled to ambient temperature and water was added. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (3×), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane—*40% dichloromethane/acetone) gave the title compound (10.67 g). HRMS 482.1999 (M+1). NMR (400 MHz, CDCl3): δ 8.57 (ddd, J=4.8, 1.8, 1.0 Hz, 1H); 8.49 (d, J=2.1 Hz, 1H); 8.45-8.39 (m, 3H); 8.16 (t, J=1.6 Hz, 1H); 7.71-7.66 (m, 2H); 7.59-7.52 (m, 3H); 7.37 (td, J=8.3, 2.8 Hz, 1H); 7.30 (dd, J=8.6, 4.4 Hz, 1H); 7.21 (ddd, J=7.6, 4.9, 1.2 Hz, 1H); 5.87 (dd, J=10.7, 7.1 Hz, 1H); 5.41-5.31 (m, 1H); 3.92-3.78 (m, 2H); 2.36 (s, 3H); 1.55 (d, J=6.8 Hz, 3H).

Workup

  1. temperaturethe mixture was cooled to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×)
  3. washThe combined organic extracts were washed with water (3×), brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% dichloromethane—*40% dichloromethane/acetone)

Sources & evidence

ORD record
ord-e21c173f13ff41a5817faa5beac41bb8
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

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