1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-4-[1,3,4]oxadiazol-2-yl-benzamide

HRID 1093773Notes

Reaction equation

HRID 1093773 reaction equation
CCN(C(C)C)C(C)C.[O:10]1[CH:14]=[N:13][N:12]=[C:11]1[C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:46][CH2:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([O:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[Cl:63])[CH2:52][CH2:51]1)=[O:49]>CN(C=O)C.O>[Cl:63][C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][C:57]=1[O:56][CH:53]1[CH2:52][CH2:51][N:50]([C:48](=[O:49])[CH2:47][NH:46][C:19](=[O:21])[C:18]2[CH:17]=[CH:16][C:15]([C:11]3[O:10][CH:14]=[N:13][N:12]=3)=[CH:23][CH:22]=2)[CH2:55][CH2:54]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 71310554-(1,3,4-oxadiazol-2-yl)benzoic AcidHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 57874515N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-4-[1,3,4]oxadiazol-2-yl-benzamideYield 38.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (203 mg, 0.27 mL, 1.57 mmol) was added to a stirred solution of 4-[1,3,4]oxadiazol-2-yl-benzoic acid (100 mg, 0.52 mmol) in DMF (2 mL) followed by HOBt (85 mg, 0.63 mmol) and EDCI (121 mg, 0.63 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (192 mg, 0.63 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to afford 88 mg (38.09% yield) of N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-4-[1,3,4]oxadiazol-2-yl-benzamide. LC/MS [M+H]+: 441.13, 95.23%. 1H NMR (300 MHz, DMSO-d6): δ 9.4 (s, 1H), 8.8 (t, 1H), 8.1 (q, 4H), 7.4 (m, 1H), 7.3 (m, 2H), 7.0 (m, 1H), 4.8 (m, 1H), 4.2 (m, 2H), 3.7 (m, 2H), 3.5 (m, 2H), 2.18 (m, 2H), 1.8-1.5 (m, 4H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. extractionthe product was extracted with EtOAc
  4. washthe organic layer was washed with brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d4274b8c15984bc8bf33a57afcca40af
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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