1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide

HRID 1093849Notes

Reaction equation

HRID 1093849 reaction equation
CCN(C(C)C)C(C)C.[N:10]1([N:16]2[CH:20]=[C:19]([C:21]([OH:23])=O)[N:18]=[N:17]2)[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.NN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:53][CH2:54][C:55]([N:57]1[CH2:62][CH2:61][CH:60]([O:63][C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([C:70]([F:73])([F:72])[F:71])[CH:65]=2)[CH2:59][CH2:58]1)=[O:56]>CN(C=O)C.O>[O:56]=[C:55]([N:57]1[CH2:58][CH2:59][CH:60]([O:63][C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([C:70]([F:73])([F:71])[F:72])[CH:65]=2)[CH2:61][CH2:62]1)[CH2:54][NH:53][C:21]([C:19]1[N:18]=[N:17][N:16]([N:10]2[CH2:11][CH2:12][O:13][CH2:14][CH2:15]2)[CH:20]=1)=[O:23]

Participants

9

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 20315N-AminomorpholineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 665919181-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid

Product 1

HCID 442350261-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amideYield 84.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (200 mg, 1.54 mmol) was added to a stirred solution of 1-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 4-aminomorpholine) (70 mg, 0.35 mmol) in DMF (5 mL) followed by HOBt (52 mg, 0.38 mmol) and EDCI (170 mg, 0.88 mmol). After 2 minutes of stirring, 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (120 mg, 0.35 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the precipitate was collected out. The solid obtained was purified by recrystallisation from a mixture of 20% ethyl acetate in hexane and MeOH to afford 144 mg (84.7% Yield) of 1-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 483.19, 92.7%. 1H NMR (300 MHz, DMSO-d6): δ 8.82 (s, 1H), 8.4 (t, 1H), 7.6 (t, 1H), 7.36 (t, 3H), 4.9 (m, 1H), 4.2 (d, 2H), 4.0-3.6 (m, 6H), 3.4 (m, 2H), 3.2 (m, 2H), 2.1 (t, 2H), 1.7 (d, 2H).

Workup

  1. customprepared by the method
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature overnight
  4. customthe precipitate was collected out
  5. customThe solid obtained
  6. customwas purified by recrystallisation from a mixture of 20% ethyl acetate in hexane and MeOH

Sources & evidence

ORD record
ord-3d80f21d052b4064b1fe38abd679001e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…