Cyclohexaneacetic acid → 2-(2-{(1S,2R)-2-[1-(cyclohexylacetyl)piperidin-4-yl]cyclopropyl}ethoxy)-5-(methylsulfonyl)pyridine

HRID 1850773Notes

Reaction equation

HRID 1850773 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[N:9][CH:10]=1)(=[O:4])=[O:3].[CH:23]1([CH2:29][C:30](O)=[O:31])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH:23]1([CH2:29][C:30]([N:20]2[CH2:21][CH2:22][CH:17]([C@H:15]3[CH2:16][C@H:14]3[CH2:13][CH2:12][O:11][C:8]3[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][N:9]=3)[CH2:18][CH2:19]2)=[O:31])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

7

Reactant 5

HCID 21363Cyclohexaneacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 708192275-(methylsulfonyl)-2-{2-[(1S,2R)-2-piperidin-4-ylcyclopropyl]ethoxy}pyridine

Product 1

HCID 708563232-(2-{(1S,2R)-2-[1-(cyclohexylacetyl)piperidin-4-yl]cyclopropyl}ethoxy)-5-(methylsulfonyl)pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 23 mg (0.071 mmol) of 5-(methylsulfonyl)-2-{2-[(1S,2R)-2-piperidin-4-ylcyclopropyl]ethoxy}pyridine in 0.6 ml anhydrous N,N-dimethylformamide at ambient temperature was added 0.020 ml (0.14 mmol) cyclohexylacetic acid, followed by 27 mg (0.14 mmol) EDCl, 9.6 mg (0.071 mmol) HOBt, and 0.062 ml (0.35 mmol) diisopropylethylamine. The solution was stirred overnight at ambient temperature. The crude in N,N-dimethylformamide was purified directly by reverse phase HPLC (TMC Pro-Pac C18; 30-100% acetonitrile/0.1% formic acid in water gradient). The pure fractions were lyophilized to yield the title compound as white solid. 1H NMR (DMSO): δ 8.65 (d, J=2.1 Hz, 1H), δ 8.15 (dd, J=8.8 Hz, 2.5 Hz, 1H), δ 7.01 (d, J=8.7 Hz, 1H), δ 4.43 (t, J=6.8 Hz, 2H), δ 4.36 (t, J=12.0 Hz, 1H), δ 3.85 (t, J=13.7 Hz, 1H), δ 3.31 (s, 1H), δ 3.28 (s, 1H), δ 3.24 (s, 3H), δ 2.94 (t, J=12.7 Hz, 1H), δ 2.15 (d, J=6.5 Hz, 2H), δ 2.00-2.04 (m, 1H), δ 1.51-1.75 (m, 9H), δ 1.08-1.23 (m, 6H), δ 0.83-0.94 (m, 3H), δ 0.53-0.59 (m, 2H). LC/MS 589.3 (M+1). GPR119 Human EC50: 11.8 nM

Workup

  1. customThe crude in N,N-dimethylformamide was purified directly by reverse phase HPLC (TMC Pro-Pac C18; 30-100% acetonitrile/0.1% formic acid in water gradient)

Sources & evidence

ORD record
ord-56ac5a485121439e9062534843f69355
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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