홈MCP워크벤치Skills
홈워크벤치알림마이페이지
llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
  1. 홈
  2. /반응

Cesium carbonate → Tert-butyl 4-(2,5-difluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-ylcarbamate

HRID 476377
노트
인쇄 미리보기

반응식

HRID 476377 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([F:15])=[CH:13][C:12]([NH:16][C:17]([C:19]3([C:22]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)=[O:23])[CH2:21][CH2:20]3)=[O:18])=[C:11]([F:32])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[C:33](=[O:40])([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH2:34].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:15][C:14]1[CH:13]=[C:12]([NH:16][C:17]([C:19]2([C:22](=[O:23])[NH:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH2:21][CH2:20]2)=[O:18])[C:11]([F:32])=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:34][C:33](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH:7]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86662871N-(4-(2-chloropyridin-4-yloxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

생성물 1

HCID 66604716Tert-butyl 4-(2,5-difluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-ylcarbamate
수율 51%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

N-(4-(2-Chloropyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (3 g, 6.5 mmol) (as prepared in Example 1), tert-butyl carbamate (2.3 g, 19.5 mmol), Xantphos (0.37 g, 0.65 mmol), and cesium carbonate (4.2 g, 13 mmol) were dissolved in dry dioxane (50 mL) and argon was bubbled through the mixture for 10 minutes. Pd2(dba)3 (0.3 g, 0.33 mmol) was then added, and the solution was sparged with argon for an additional 10 minutes. The flask was fitted with a reflux condenser and a balloon of argon and slowly heated to 100° C. and stirred overnight. The reaction mixture was cooled to RT. It was diluted with ethyl acetate (100 mL) and water (80 mL). The organic layer was separated and washed with brine. The aqueous layer was back extracted with the ethyl acetate, which was then washed with brine. The combined organic layers were dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography to give tert-butyl 4-(2,5-difluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-ylcarbamate (1.8 g, 51% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.03 (s, 1H), 9.88 (s, 1H), 9.78 (s, 1H), 8.13-8.05 (m, 2H), 7.59-7.53 (m, 3H), 7.33 (d, J=2.4 Hz, 1H), 7.18-7.13 (m, 2H), 6.63 (d, J=2.4 Hz, 1H), 1.63-1.62 (m, 2H), 1.58-1.56 (m, 2H), 1.40 (s, 9H).

후처리

  1. customargon was bubbled through the mixture for 10 minutes
  2. customthe solution was sparged with argon for an additional 10 minutes
  3. customThe flask was fitted with a reflux condenser
  4. temperatureThe reaction mixture was cooled to RT
  5. additionIt was diluted with ethyl acetate (100 mL) and water (80 mL)
  6. customThe organic layer was separated
  7. washwashed with brine
  8. extractionThe aqueous layer was back extracted with the ethyl acetate, which
  9. washwas then washed with brine
  10. dry with materialThe combined organic layers were dried over sodium sulfate
  11. customevaporated
  12. customThe residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-6e84331d2bf14659b5ad1b5ad6a34be3
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08637672B2

반응 노트

불러오는 중…

이 페이지에서참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트