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

HRID 1850773ノート

反応式

HRID 1850773 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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

後処理

  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)

出典と根拠

ORDレコード
ord-56ac5a485121439e9062534843f69355
出典データセット
uspto-grants-2015_02
特許番号
US08957062B2

反応ノート

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