1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-1-(2-pyridyl)cyclopentanecarboxamide

HRID 30394Notes

Reaction equation

HRID 30394 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1([C:12]([O:14]CC2C=CC=CC=2)=O)[CH2:11][CH2:10][CH2:9][CH2:8]1.O.[OH-].[Li+].Cl.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH:34]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:35]([NH2:37])[CH3:36])=[CH:29][CH:28]=1.CN(C)CCCN=C=NCC>C(#N)C.O.CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([CH2:33][CH:34]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:35]([NH:37][C:12]([C:7]2([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH2:8][CH2:9][CH2:10][CH2:11]2)=[O:14])[CH3:36])=[CH:31][CH:32]=1

Participants

10

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 168937Lithium hydroxide, monohydrateHCID 22270502N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-amine hydrochlorideHCID 858716721-(2-Pyridyl)cyclopentanecarboxylic acid, benzyl ester

Product 1

HCID 10194828N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-1-(2-pyridyl)cyclopentanecarboxamide

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 1-(2-pyridyl)cyclopentanecarboxylic acid, benzyl ester-(Step A, 0.20 g, 0.71 mmol) in acetonitrile (3 mL) and water (1.5 mL) was added lithium hydroxide monohydrate (0.24 g, 5.6 mmol). After stirring at room temperature for 5 h and 50° C. overnight, the reaction mixture was concentrated to dryness. The residue was azeotroped with toluene and was suspended in methylene chloride (6 mL) and dimethylformamide (3 mL), and was added N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-amine hydrochloride (Diastereomer α, Reference Example 2, 0.40 g, 0.14 mm), 4-dimethylaminopyridine (0.10 g, 0.71 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (38 mg, 0.19 mmol). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water and brine, dried over anhydrous sodium sulfate and concentrated to dryness. N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-1-(2-pyridyl)cyclopentanecarboxamide was obtained by flash column chromatography on silica gel eluted with 15-20% ethyl acetate in hexane. 1H NMR (400 MHz, CD3OD): δ 8.52 (d, 1H), 7.77 (t, 1H), 7.48 (d, 1H), 7.35-7.08 (m, 4H), 7.00 (d, 2H), 6.94 (d, 2H), 6.68 (d, 2H), 4.20 (m, 1H), 2.80 (dd, 1H), 2.73 (m, 1H), 2.60 (m, 2H), 2.45 (m, 1H), 2.30 (m, 1H), 2.18 (m, 1H), 1.85-1.65 (m, 4H), 0.82 (d, 3H). LC-MS: m/e 433 (M+H)+ (3.2 min).

Workup

  1. concentrationthe reaction mixture was concentrated to dryness
  2. customThe residue was azeotroped with toluene
  3. stirringAfter stirring at room temperature overnight
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-c5bb5e90a98e4caabb8699a14c4d3abf
Source dataset
uspto-grants-2008_09
Patent number
US07423067B2

Reaction notes

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