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

Citric Acid → (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(pyridin-2-yl)propanamide

HRID 1098232
노트
인쇄 미리보기

반응식

HRID 1098232 반응식
[H-].[Na+].[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([OH:35])[C:26]([NH:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1)=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:37]1[N:42]=[CH:41][N:40]=[C:39]2[N:43]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=3[Cl:52])[N:44]=[CH:45][C:38]=12.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([O:35][C:37]1[N:42]=[CH:41][N:40]=[C:39]2[N:43]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=3[Cl:52])[N:44]=[CH:45][C:38]=12)[C:26]([NH:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1)=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidine2회HCID 57504689(S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxy-N-(pyridin-2-yl)propanamide2회

생성물 1

HCID 57504548(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(pyridin-2-yl)propanamide
수율 95.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

Sodium hydride (91 mg, 2.27 mmol) was added to (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxy-N-(pyridin-2-yl)propanamide (Intermediate AQ4) (480 mg, 1.03 mmol) (intermediate 3) in anhydrous THF (20 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B1) (320 mg, 1.14 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was neutralised with 1M citric acid and the majority of the THF removed in vacuo. The reaction mixture was diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2×100 mL). The combined organics were washed with saturated brine (75 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 50 to 100% EtOAc in isohexane to afford the product (682 mg, 95%). 1H NMR: (400 MHz, CDCl3) δ 0.98-1.00 (9H, m), 3.69-3.72 (2H, m), 3.81 (2H, t), 4.16-4.25 (2H, m), 6.06-6.09 (1H, m), 7.04-7.07 (1H, m), 7.31-7.66 (14H, m), 7.68-7.73 (1H, m), 8.24-8.28 (2H, m), 8.38 (1H, s), 8.58 (1H, s), 8.75 (1H, s); m/z (ES+) M+=693.61; HPLC tR=3.79 min.

후처리

  1. temperatureto warm to room temperature
  2. stirringstirred for 1 hour
  3. customthe majority of the THF removed in vacuo
  4. additionThe reaction mixture was diluted with water (20 mL) and EtOAc (50 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer re-extracted with EtOAc (2×100 mL)
  7. washThe combined organics were washed with saturated brine (75 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography
  11. washeluting with 50 to 100% EtOAc in isohexane

출처 및 근거

ORD 기록
ord-6f4e0c2174ad431d8c577de46e3835bc
출처 데이터셋
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08143263B2

반응 노트

불러오는 중…

이 페이지에서참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트