Potassium Carbonate → 5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amine

HRID 1049273노트

반응식

HRID 1049273 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:16][N:17]1[CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=[N:18]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:16][N:17]1[CH:21]=[C:20]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[N:11][C:12]([NH2:15])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:19]=[N:18]1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 904034955-((2-Chloropyridin-4-yl)oxy)pyrimidin-2-amine

생성물 1

HCID 904034835-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amine수율 55.8%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
85 °C

실험 절차

5-((2-chloropyridin-4-yl)oxy)pyrimidin-2-amine (676 mg, 3.04 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (758 mg, 3.64 mmol), potassium carbonate (1.259 g, 9.11 mmol) and Pd(PPh3)4 (175 mg, 0.152 mmol) were combined in dioxane (12 mL) and water (3 mL). The mixture was degassed with argon, and warmed to 85° C. overnight. The mixture was diluted with EtOAc (75 mL) and water (40 mL) and was filtered to collect an off-white solid. The organic phase was separated, washed with brine (40 mL) and evaporated at reduced pressure to give additional off-white solid. The two crops of solids were combined and triturated with EtOAc (15 mL) with sonication. The solid was collected by filtration, washed with EtOAc (2×5 mL) and dried under vacuum to provide 5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amine (455 mg, 55%). 1H NMR (DMSO-d6): δ 8.34 (d, J=5.7 Hz, 1H), 8.26 (s, 1H), 8.22 (s, 2H), 7.96 (s, 1H), 7.19 (d, J=2.4 Hz, 1H), 6.77 (s, 2H), 6.67 (dd, J=5.7, 2.5 Hz, 1H), 3.84 (s, 3H); MS (ESI) m/z: 269.1 (M+H+).

후처리

  1. customThe mixture was degassed with argon
  2. additionThe mixture was diluted with EtOAc (75 mL) and water (40 mL)
  3. filtrationwas filtered
  4. customto collect an off-white solid
  5. customThe organic phase was separated
  6. washwashed with brine (40 mL)
  7. customevaporated at reduced pressure
  8. customto give additional off-white solid
  9. customtriturated with EtOAc (15 mL) with sonication
  10. filtrationThe solid was collected by filtration
  11. washwashed with EtOAc (2×5 mL)
  12. customdried under vacuum

출처 및 근거

ORD 기록
ord-4126eb3fe298440ebe9346e9301f3003
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382228B2

반응 노트

불러오는 중…