3-Amino-6-chloro-4-picoline → 4-[6-(6-Chloro-4-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 1036779노트

반응식

HRID 1036779 반응식
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+].[Cl:28][C:29]1[N:34]=[CH:33][C:32]([NH2:35])=[C:31]([CH3:36])[CH:30]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C2C=CC=CC=2)C=CC=C(P(C(C)(C)C)C(C)(C)C)C=1>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([NH:35][C:32]3[CH:33]=[N:34][C:29]([Cl:28])=[CH:30][C:31]=3[CH3:36])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

참가 물질

7

반응물 3

HCID 27344253-Amino-6-chloro-4-picolineHCID 114933574-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl esterHCID 23676156Sodium t-butoxide

생성물 1

HCID 114642744-[6-(6-Chloro-4-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester수율 29.1%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 67201513Biphenyl-3-yl-di-tert-butyl-phosphane촉매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

A mixture of 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (1.80 g, 5.74 mmol), palladium acetate (155 mg, 0.69 mmol), biphenyl-3-yl-di-tert-butyl-phosphane (21.5 mg, 0.072 mmol), sodium tert-butoxide (1.38 g, 14.4 mmol), and 6-chloro-4-methyl-pyridin-3-ylamine (838 mg, 5.80 mmol) in 20 mL dioxane was heated in microwave for 1 hour at 120° C. Solids were filtered off and mixture was purified by column chromatography (hexane/AcOEt) to give Compound A98 as a tanned solid (702 mg, 29%). 1H NMR (CDCl3, 400 MHz) δ 1.24-1.26 (d, 6H), 1.72-1.81 (m, 2H), 1.95-2.02 (m, 2H), 2.10 (s, 3H), 2.27 (s, 3H), 3.37-3.43 (m, 2H), 3.74-3.77 (m, 2H), 4.90-4.97 (m, 1H), 5.29-5.34 (m, 1H), 5.91 (s, 1H), 7.00 (s, 1H), 8.22 (s, 1H), 8.57 (s, 1H). Exact mass calculated for C20H26ClN5O3 419.17, found 420.4 (MH+).

후처리

  1. filtrationSolids were filtered off
  2. custommixture was purified by column chromatography (hexane/AcOEt)

출처 및 근거

ORD 기록
ord-0727b16a84d64597bb1dd5b9c77dddfd
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546429B2

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