2-Phenylpropionic acid → N-(2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-2-phenyl-propionamide

HRID 1042059Notes

Reaction equation

HRID 1042059 reaction equation
[C:1]1([CH:7]([CH3:11])[C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:48][C:49]1[N:50]=[C:51]([CH:54]2[CH2:59][CH2:58][N:57]([C:60](=[O:70])[CH2:61][C:62]3[CH:67]=[C:66]([CH3:68])[CH:65]=[CH:64][C:63]=3[CH3:69])[CH2:56][CH2:55]2)[S:52][CH:53]=1>C(#N)C>[CH3:69][C:63]1[CH:64]=[CH:65][C:66]([CH3:68])=[CH:67][C:62]=1[CH2:61][C:60]([N:57]1[CH2:56][CH2:55][CH:54]([C:51]2[S:52][CH:53]=[C:49]([NH:48][C:8](=[O:10])[CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH3:11])[N:50]=2)[CH2:59][CH2:58]1)=[O:70]

Participants

6

Reactant 4

HCID 102962-Phenylpropionic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 669555241-[4-(4-Amino-thiazol-2-yl)-piperidin-1-yl]-2-(2,5-dimethyl-phenyl)-ethanone

Product 1

HCID 66956445N-(2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-2-phenyl-propionamideYield 13.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (rac.)-2-phenylpropionic acid (46 mg, 0.30 mmol) and diisopropylethylamine (0.15 mL, 0.9 mmol) in acetonitrile (2 mL) is added benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (322 mg, 0.73 mmol) at RT. After stirring 30 min at RT, 1-[4-(4-amino-thiazol-2-yl)-piperidin-1-yl]-2-(2,5-dimethyl-phenyl)-ethanone (100 mg, 0.30 mmol) is added to the reaction mixture. After stirring overnight at RT, the solvent is evaporated and the residue is purified by flash chromatography on silica gel (ethylacetate/cyclohexane 1:1) to give N-(2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-2-phenyl-propionamide (Compound No. I.g.141, 19 mg, 13.4%). 1H-NMR (400 MHz, CDCl3): δ=1.46-1.39 (m, 1H), 1.52 (d, 3H), 1.68-1.56 (m, 1H), 1.89-1.83 (m, 1H), 2.01-1.97 (m, 1H), 2.15 (s, 3H), 2.19 (s, 3H), 2.73-2.67 (m, 1H), 3.18-2.92 (m, 2H), 3.59 (s, 2H), 3.68-3.63 (q, 1H), 3.78-3.71 (m, 1H), 4.65-4.62 (m, 1H), 6.91-6.82 (m, 2H), 7.02-6.98 (m, 1H), 7.31-7.15 (m, 5H), 7.42 (s, 1H), 8.05 (br, 1H). MS: m/z=462 (M+1).

Workup

  1. stirringAfter stirring overnight at RT
  2. customthe solvent is evaporated
  3. customthe residue is purified by flash chromatography on silica gel (ethylacetate/cyclohexane 1:1)

Sources & evidence

ORD record
ord-05cd72285c7b4eb6b7440034de06883b
Source dataset
uspto-grants-2013_10
Patent number
US08557821B2

Reaction notes

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