Lithium Hexamethyldisilazide → N-(5-bromo-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine

HRID 1811849노트

반응식

HRID 1811849 반응식
[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[N:17]=[C:16]([CH3:18])[N:15]=[C:14]3[C:10]=2[N:11]=[CH:12][N:13]3[CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[C:5](F)=[N:6][CH:7]=1.[O:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]1[N:31]1[C:39]2[CH:38]=[CH:37][CH:36]=[C:35]([NH2:40])[C:34]=2[CH:33]=[N:32]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[N:17]=[C:16]([CH3:18])[N:15]=[C:14]3[C:10]=2[N:11]=[CH:12][N:13]3[CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[C:5]([NH:40][C:35]2[C:34]3[CH:33]=[N:32][N:31]([CH:26]4[CH2:27][CH2:28][CH2:29][CH2:30][O:25]4)[C:39]=3[CH:38]=[CH:37][CH:36]=2)=[N:6][CH:7]=1

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 441182321-(Oxan-2-yl)-1H-indazol-4-amineHCID 595484646-(5-bromo-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

생성물 1

HCID 66611987N-(5-bromo-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

A solution of 6-(5-bromo-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (0.250 g, 0.637 mmol) and 1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (0.138 g, 0.637 mmol) in THF (10 mL) was stirred at 0° C. and treated dropwise with lithium bis(trimethylsilyl)amide, 1.0 M solution in THF (1.912 mL, 1.912 mmol) (Aldrich catalog number 225770) and stirred at 0° C. for 30 minutes. The mixture was quenched with water (10 mL), diluted with water (50 mL) and extracted with dichloromethane. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (40 g), eluting with a gradient of 5% to 10% 2 M NH3/MeOH in dichloromethane to give N-(5-bromo-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine as yellow crystals. This was treated with dichloromethane (5 mL) and trifluoroacetic acid (5 mL) (Aldrich, St. Louis, Mo.) to give N-(5-bromo-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indazol-4-amine, m/z (ESI, +ve) 421/423 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 13.75 (br. s., 1H); 13.25 (br. s., 1H); 12.85 (br. s., 1H); 8.69 (br. s., 1H); 8.48 (br. s., 1H); 7.99 (br. s., 1H); 7.32 (br. s., 1H); 7.23 (br. s., 1H); 2.93 (s, 3H).

후처리

  1. customThe mixture was quenched with water (10 mL)
  2. additiondiluted with water (50 mL)
  3. extractionextracted with dichloromethane
  4. custompurified by chromatography through a RediSep®, Teledyne ISCO, Lincoln, Nebr
  5. wash, pre-packed silica gel column (40 g), eluting with a gradient of 5% to 10% 2 M NH3/MeOH in dichloromethane

출처 및 근거

ORD 기록
ord-ed0a4afe55cc427f90865ec811cca6ba
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362241B2

반응 노트

불러오는 중…