1,2-Dichloroethane → HCID 178423796, compound

HRID 1257552Notes

Reaction equation

HRID 1257552 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]3[CH2:21][C:17]4([CH2:20][CH2:19][CH2:18]4)[O:16][N:15]=3)[CH:11]=[C:10]([C:22](O)=[O:23])[CH:9]=2)=[CH:4][CH:3]=1.Cl.[N:26]1[N:27]=[C:28]([C@@H:31]([NH2:33])[CH3:32])[NH:29][CH:30]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[C:12]([C:14]3[CH2:21][C:17]4([CH2:20][CH2:19][CH2:18]4)[O:16][N:15]=3)[CH:11]=[C:10]([C:22]([NH:33][C@H:31]([C:28]3[NH:29][CH:30]=[N:26][N:27]=3)[CH3:32])=[O:23])[CH:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 668957974'-Methyl-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)biphenyl-3-carboxylic acidHCID 178462005HCID 178462005, compound

Product 1

HCID 178423796HCID 178423796, compoundYield 96.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4′-methyl-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)biphenyl-3-carboxylic acid (0.15 g, 0.47 mmol) in N,N-dimethylformamide (3 mL) were added (1S)-1-(4H-1,2,4-triazol-3-yl)ethanamine hydrochloride salt (0.12 g, 0.65 mmol), EDC (0.13 g, 0.70 mmol), HOAT (0.06 g, 0.47 mmol) and triethylamine (0.39 mL, 2.80 mmol). The reaction mixture was heated to 50° C. After 1 h, the mixture was cooled to ambient temperature. Saturated aqueous NaHCO3 was added and 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→90% dichloromethane/methanol) gave the title compound (188 mg). The title compound was dissolved in dichloromethane and HCl (2.0 M in ether) was added. The mixture was concentrated gave the hydrochloride salt of the title compound. HRMS 416.2083 (M+1). 1H NMR (400 MHz, CD3OD): δ 9.35 (s, 1H); 8.16 (t, J=1.7 Hz, 1H); 8.11 (t, J=1.6 Hz, 1H); 8.03 (t, J=1.7 Hz, 1H); 7.56 (d, J=7.9 Hz, 2H); 7.26 (d, J=7.8 Hz, 2H); 5.54-5.44 (m, 1H); 3.69-3.45 (m, 2H); 2.52-2.42 (m, 2H); 2.35 (s, 3H); 2.30-2.22 (m, 2H); 1.77 (d, J=7.1 Hz, 2H).

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→90% dichloromethane/methanol)

Sources & evidence

ORD record
ord-0e3934ce350b4e1587adedb050012238
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

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