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 1748829노트

반응식

HRID 1748829 반응식
[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]

참가 물질

4

반응물 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

생성물 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-enoate수율 99%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  1. concentrationthen concentrated in vacuo

출처 및 근거

ORD 기록
ord-a08976db2c8249e5bbf4bb1eed2d31b8
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150592B2

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