1-Hydroxybenzotriazole → 1-[4-(2-Chloro-phenoxy)-piperidine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamide

HRID 1093710Notes

Reaction equation

HRID 1093710 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.Cl.[Cl:33][C:34]1[CH:46]=[CH:45][CH:44]=[CH:43][C:35]=1[O:36][CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.[C:47]1([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH:52]=[CH:51][C:50]([NH:53][C:54]([C:56]2([C:59](O)=[O:60])[CH2:58][CH2:57]2)=[O:55])=[CH:49][CH:48]=1>CN(C=O)C.O>[C:47]1([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)[CH:52]=[CH:51][C:50]([NH:53][C:54]([C:56]2([C:59]([N:40]3[CH2:41][CH2:42][CH:37]([O:36][C:35]4[CH:43]=[CH:44][CH:45]=[CH:46][C:34]=4[Cl:33])[CH2:38][CH2:39]3)=[O:60])[CH2:58][CH2:57]2)=[O:55])=[CH:49][CH:48]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167325894-(2-Chlorophenoxy)piperidine hydrochlorideHCID 578743681-(Biphenyl-4-ylcarbamoyl)-cyclopropanecarboxylic acid

Product 1

HCID 578744051-[4-(2-Chloro-phenoxy)-piperidine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamideYield 46.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HOBt (57 mg, 0.42 mol) and DIPEA (137 mg, 1.06 mmole), EDCI.HCl (82 mg, 0.42 mol) followed by 4-(2-chloro-phenoxy)-piperidine hydrochloride (105 mg, 0.42 mol) were added to a stirred solution of 1-(biphenyl-4-ylcarbamoyl)-cyclopropanecarboxylic acid (100 mg, 0.35 mmol) in DMF (2.0 mL) and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with water. The product was extracted with ethylacetate and the organic layers were washed with brine and concentrated to afford 78 mg (46%) of 1-[4-(2-chloro-phenoxy)-piperidine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamide. LCMS: 475.17 (M+1)+, 92.81%, 1H NMR (DMSO-d6): δ 9.8 (s, 1H), 7.8-7.5 (d, 2H), 7.7-7.6 (t, 4H), 7.5-7.4 (m, 3H), 7.4-7.2 (m, 3H), 7.0-6.9 (m, 1H), 4.7 (m, 1H), 3.8-3.6 (m, 2H), 3.5 (m, 2H), 2.0-1.8 (m, 2H), 1.7-1.6 (m, 2H), 1.4 (m, 2H), 1.3-1.2 (m, 2H).

Workup

  1. extractionThe product was extracted with ethylacetate
  2. washthe organic layers were washed with brine
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-e15f35ba89194eb7930d3920ec271ae0
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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