Tert-Butylamine → 2-methylpropan-2-aminium (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoate

HRID 1748829ノート

反応式

HRID 1748829 の反応式
[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:3]=1/[C:14](/[C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[CH3:27])=[CH:15]\[CH2:16][C:17]([OH:19])=[O:18].[CH3:28][C:29]([NH2:32])([CH3:31])[CH3:30]>C1COCC1>[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:3]=1/[C:14](/[C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[CH3:27])=[CH:15]\[CH2:16][C:17]([O-:19])=[O:18].[CH3:28][C:29]([NH3+:32])([CH3:31])[CH3:30]

参加物

4

反応物 2

HCID 6385Tert-ButylamineHCID 86724151(Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoic acid

生成物 1

HCID 867241522-methylpropan-2-aminium (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoate収率 99%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (Z)-methyl 4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoate (13.34 g, 32.0 mmol) in dioxane (150 mL) was added 2 N aqueous NaOH (32 mL, 64 mmol). The mixture was stirred at rt for about 16 h then partitioned between EtOAc (300 mL) and 10% citric acid (200 mL). The layers were separated and the aqueous layer was extracted with EtOAc (300 mL). The combined organic layers were washed with water (300 mL) followed by brine (300 mL) then concentrated in vacuo. The residue was triturated in Et2O to give (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoic acid (12.31 g, 95%) as an off-white solid: LC-MS (Table 1, Method g) Rt=2.20 min, m/z 402/404 (M+H)+; 1H-NMR (DMSO, Bruker 400 MHz) δ 12.18 (s, 1H), 8.42-8.39 (m, 1H), 7.80-7.68 (m, 2H), 7.26-7.19 (m, 1H), 7.16 (d, J=2.2 Hz, 1H), 7.08-7.04 (m, 1H), 7.01-6.97 (m, 1H), 5.91 (t, J=7.2 Hz, 1H), 3.92 (s, 3H), 2.95 (s, 2H), 2.34 (s, 3H). To a suspension of (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoic acid (12.31 g, 30.6 mmol) in THF (50 mL) was added 2-methylpropan-2-amine (6.46 mL, 61.2 mmol). The mixture was stirred at rt for about 10 min then concentrated in vacuo to give 2-methylpropan-2-aminium (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoate (14.40 g, 95%): LC-MS (Table 1, Method g) Rt=2.20 min, m/z 402/404 (M+H)+; 1H-NMR (DMSO, Bruker 400 MHz) δ 8.41-8.38 (m, 1H), 7.78-7.67 (m, 2H), 7.24-7.17 (m, 1H), 7.13 (d, J=2.1 Hz, 1H), 7.05-7.01 (m, 1H), 6.99-6.96 (m, 1H), 6.01 (t, J=7.1 Hz, 1H), 3.91 (s, 3H), 2.81-2.59 (m, 2H), 2.32 (s, 3H), 1.16 (s, 9H).

後処理

  1. concentrationthen concentrated in vacuo

出典と根拠

ORDレコード
ord-a08976db2c8249e5bbf4bb1eed2d31b8
出典データセット
uspto-grants-2015_10
特許番号
US09150592B2

反応ノート

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