1,2-Dichloroethane → 2-[4-(3-cyclopropylpyrazin-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

HRID 474152Notes

Reaction equation

HRID 474152 reaction equation
[CH:1]1([C:4]2[C:5]([C:10]3[CH:15]=[CH:14][C:13]([CH2:16][C:17]([OH:19])=O)=[CH:12][CH:11]=3)=[N:6][CH:7]=[CH:8][N:9]=2)[CH2:3][CH2:2]1.[Cl-].[Cl-].[NH3+:22][C@@H:23]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]([F:36])([F:35])[F:34])=[CH:27][NH+:26]=1)[CH3:24].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:1]1([C:4]2[C:5]([C:10]3[CH:11]=[CH:12][C:13]([CH2:16][C:17]([NH:22][C@@H:23]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]([F:36])([F:34])[F:35])=[CH:27][N:26]=4)[CH3:24])=[O:19])=[CH:14][CH:15]=3)=[N:6][CH:7]=[CH:8][N:9]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 59535939[4-(3-Cyclopropylpyrazin-2-yl)phenyl]acetic acidHCID 178462209HCID 178462209, compound

Product 1

HCID 426100152-[4-(3-cyclopropylpyrazin-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamideYield 73.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.080 g (0.32 mmol) of ([4-(3-cyclopropylpyrazin-2-yl)phenyl]acetic acid in 1.00 ml DMF was added 0.11 g (0.38 mmol) of 2-[(1R)-1-ammonioethyl]-5-(2,2,2-trifluoroethoxy)pyridinium dichloride, 0.056 g (0.41 mmol) of HOAt, 0.078 g (0.41 mmol) of EDC, and 0.17 mL (0.94 mmol) of DIEA. After 12 h at room temperature, the reaction mixture was purified by reverse-phase preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18) to afford 0.13 g (73.8%) of 2-[4-(3-cyclopropylpyrazin-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide. 1H NMR (CDCl3, 400 MHz) δ 8.36 (s, 2H); 8.27 (d, J=2.74 Hz, 1H); 7.68 (d, J=8.15 Hz, 2H); 7.40 (d, J=8.06 Hz, 2H); 7.34 (m, 2H); 7.20 (d, J=5.95 Hz, 1H); 5.15 (m, 1H); 4.41 (dd, J=7.88, 15.84 Hz, 2H); 3.65 (s, 2H); 2.22 (m, 1H); 1.46 (d, J=6.95, 3H); 1.19 (m, 2H); 0.99 (m, 2H). HRMS (ES) [M+1]+calcd for C24H24F3N4O2: 457.1851, Found: 457.1831. FLIPR alpha1I IP=47 nM.

Workup

  1. customthe reaction mixture was purified by reverse-phase preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18)

Sources & evidence

ORD record
ord-53869aff923d4b4a9db31c4af346ac94
Source dataset
uspto-grants-2014_01
Patent number
US08637513B2

Reaction notes

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