1,2-Dichloroethane → HCID 178423797, compound

HRID 1257536Notes

Reaction equation

HRID 1257536 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([C:15]2[CH2:19][C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[O:17][N:16]=2)[CH:12]=[C:11]([C:26]([OH:28])=O)[CH:10]=1.Cl.[N:30]1[N:31]=[C:32]([C@@H:35]([NH2:37])[CH3:36])[NH:33][CH:34]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C)C=O.O>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([C:15]2[CH2:19][C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[O:17][N:16]=2)[CH:12]=[C:11]([C:26]([NH:37][C@H:35]([C:32]2[NH:33][CH:34]=[N:30][N:31]=2)[CH3:36])=[O:28])[CH:10]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 668959112'-fluoro-4'-methyl-5-[(5S)-5-(2-pyridinyl)-4,5-dihydro-3-isoxazolyl]-3-biphenylcarboxylic acidHCID 178462005HCID 178462005, compound

Product 1

HCID 178423797HCID 178423797, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2′-fluoro-4′-methyl-5-[(5S)-5-(2-pyridinyl)-4,5-dihydro-3-isoxazolyl]-3-biphenylcarboxylic acid (125 mg, 0.227 mmol) in N,N-dimethylformamide (1 mL) were added (1S)-1-(4H-1,2,4-triazol-3-yl)ethanamine hydrochloride salt (52 mg, 0.283 mmol), EDC (65 mg, 0.340 mmol), HOAT (9 mg, 0.068 mmol) and triethylamine (95 μL, 0.680 mmol). The reaction mixture was stirred at ambient temperature for 18 h. Water was added. Purification by reverse phase HPLC(C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% ammonium hydroxide), and concentration gave the free base. Concentrate was taken up in dichloromethane into which hydrogen chloride gas was bubbled. Concentration gave the title compound as the hydrochloride salt (94.0 mg). HRMS 471.1977 (M+1). 1H NMR (500 MHz, CD 30D): δ 8.94 (s, 1H); 8.78 (d, J=5.6 Hz, 1H); 8.53 (t, J=7.7 Hz, 1H); 8.25 (t, J=1.7 Hz, 1H); 8.16 (t, J=1.6 Hz, 1H); 8.11-8.07 (m, 2H); 7.94 (t, J=6.6 Hz, 1H); 7.46 (t, J=7.9 Hz, 1H); 7.15-7.07 (m, 2H); 6.18 (dd, J=11.4, 6.6 Hz, 1H); 5.50-5.45 (m, 1H); 4.21 (dd, J=17.3, 11.5 Hz, 1H); 3.86 (dd, J=20.8, 7.9 Hz, 1H); 2.41 (s, 3H); 1.74 (d, J=7.1 Hz, 3H).

Workup

  1. customPurification by reverse phase HPLC(C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% ammonium hydroxide), and
  2. concentrationconcentration
  3. customgave the free base
  4. concentrationConcentrate
  5. customwas bubbled
  6. concentrationConcentration

Sources & evidence

ORD record
ord-02b8e6b9e2a14a6780af43d54fd565fd
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

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