2-Fluoro-4-iodoaniline → 4-[6-(2-Fluoro-4-iodo-phenylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 1036773노트

반응식

HRID 1036773 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+].[I:28][C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[C:31]([F: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:33][C:32]3[CH:34]=[CH:35][C:29]([I:28])=[CH:30][C:31]=3[F: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 1856942-Fluoro-4-iodoanilineHCID 114933574-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl esterHCID 23676156Sodium t-butoxide

생성물 1

HCID 598568514-[6-(2-Fluoro-4-iodo-phenylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester수율 47.1%

시약·촉매·용매 3

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

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온도
120 °C

실험 절차

A mixture of 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (2.58 g, 8.22 mmol), palladium acetate (185 mg, 0.82 mmol), biphenyl-3-yl-di-tert-butyl-phosphane (25 mg, 0.08 mmol), sodium tert-butoxide (2.4 g, 21.2 mmol), and 4-iodo-2-fluoro aniline (2.0 g, 8.4 mmol) in 15 mL dioxane was heated in microwave for 1 hour at 120° C. Solids were filtered off and mixture was purified by column chromatography and precipitating out of hexane/AcOEt to give compound A77 as a tanned solid (1.99 g, 47%). 1H NMR (CDCl3, 400 MHz) δ 1.15-1.16 (d, 6H), 1.61-1.71 (m, 2H), 1.85-1.90 (m, 2H), 1.99 (s, 3H), 3.27-3.33 (m, 2H), 3.63-3.66 (m, 2H), 4.82-4.85 (m, 1H), 5.20-5.23 (m, 1H), 6.35-6.36 (d, 1H), 7.33-7.36 (m, 2H), 8.08-8.13 (m, 1H), 8.22 (s, 1H). Exact mass calculated for C20H24F1N4O3 514.09, found 515.2 (MH+).

후처리

  1. filtrationSolids were filtered off
  2. custommixture was purified by column chromatography
  3. customprecipitating out of hexane/AcOEt

출처 및 근거

ORD 기록
ord-dea69f6c91e94c76ad0326faa4ed9d1b
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546429B2

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