1,2-Dichloroethane → N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-3-(5-methylpyridin-2-yl)-5-(2-methylpyrimidin-5-yl)benzamide

HRID 888396Notes

Reaction equation

HRID 888396 reaction equation
[Cl-].[Na+].[CH3:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:11]=[C:12]([CH:16]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([CH3:25])=[N:23][CH:24]=3)[CH:18]=2)[C:13](O)=[O:14])=[N:8][CH:9]=1.[CH3:26][C:27]1[N:31]=[C:30]([C@H:32]([NH2:34])[CH3:33])[O:29][N:28]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.FC(F)(F)C(O)=O>CN(C)C=O.O>[CH3:26][C:27]1[N:31]=[C:30]([C@H:32]([NH:34][C:13](=[O:14])[C:12]2[CH:16]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([CH3:25])=[N:23][CH:24]=3)[CH:18]=[C:10]([C:7]3[CH:6]=[CH:5][C:4]([CH3:3])=[CH:9][N:8]=3)[CH:11]=2)[CH3:33])[O:29][N:28]=1

Participants

10

Reactant 7

HCID 111,2-DichloroethaneHCID 5234Sodium ChlorideHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 28948822(R)-1-(3-Methyl-1,2,4-oxadiazol-5-yl)ethan-1-amineHCID 684984603-(5-Methylpyridin-2-yl)-5-(2-methylpyrimidin-5-yl)benzoic acid

Product 1

HCID 42602996N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-3-(5-methylpyridin-2-yl)-5-(2-methylpyrimidin-5-yl)benzamideYield 95.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the sodium chloride salt of 3-(5-methylpyridin-2-yl)-5-(2-methylpyrimidin-5-yl)benzoic acid (35 mg, 0.073 mmol) in N,N-dimethylformamide (0.728 mL) was added the hydrochloride salt of (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine (17.5 mg, 0.087 mmol), EDC (16.8 mg, 0.087 mmol), HOBT (11.2 mg, 0.073 mmol), and triethylamine (0.041 mL, 0.291 mmol). After 16 h, water and trifluoroacetic acid were added. Purification by reverse phase chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (28.8 mg). HRMS 415.1880 (M+1). 1H NMR (500 MHz, CD3OD): δ 9.21 (s, 2H); 8.78 (s, 1H); 8.57-8.53 (m, 2H); 8.49 (d, J=9.5 Hz, 2H); 8.42 (d, J=8.3 Hz, 1H); 5.51 (q, J=7.2 Hz, 1H); 2.80 (s, 3H); 2.64 (s, 3H); 2.37 (s, 3H); 1.75 (d, J=7.1 Hz, 3H).

Workup

  1. customPurification by reverse phase chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-c25fb91eb1aa4578bbb0c5de73cd2302
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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