Potassium Carbonate → 9-benzyloxy-6-(4-chloro-2-pyridin-3-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169421노트

반응식

HRID 2169421 반응식
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2Br)[N:11]2[CH2:25][CH2:26][N:27]([CH:30]([CH3:32])[CH3:31])[C:28](=[O:29])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35](B(O)O)[CH:34]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCOCC1>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[C:35]2[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=2)[N:11]2[CH2:25][CH2:26][N:27]([CH:30]([CH3:32])[CH3:31])[C:28](=[O:29])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 867260459-benzyloxy-6-(2-bromo-4-chlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

생성물 1

HCID 867260539-benzyloxy-6-(4-chloro-2-pyridin-3-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione수율 50.1%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

In a sealed tube was placed a stirred solution of 9-benzyloxy-6-(2-bromo-4-chlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (380) (100 mg, 0.194 mmol) in dioxane (3 mL). Pyridine 3-boronic acid (23.822 mg, 0.194 mmol), and a 1N solution of potassium carbonate [(80.349 mg, 0.581 mmol) dissolved in 1.25 mL water] were added at room temperature, and the reaction mixture was purged with argon for 30 min. Then, Pd(triphenyl phosphine)4 (22.395 mg, 0.019 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (15.911 mg, 0.039 mmol) were added and the reaction mixture was further degassed for another 10 min. The reaction mixture was heated at 80° C. for 4 h (monitored by LC-MS). The reaction mixture was filtered through a pad of cellite and the filtrate was diluted with water (5 mL) and extracted with ethyl acetate (2×20 mL). The combined extracts were dried and concentrated. The resulting crude product was purified by column (using amine bound silica gel) to get 9-benzyloxy-6-(4-chloro-2-pyridin-3-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (389) (50 mg, 50.1%) as an off-white solid.

후처리

  1. customIn a sealed tube was placed
  2. customthe reaction mixture was purged with argon for 30 min
  3. customthe reaction mixture was further degassed for another 10 min
  4. filtrationThe reaction mixture was filtered through a pad of cellite
  5. additionthe filtrate was diluted with water (5 mL)
  6. extractionextracted with ethyl acetate (2×20 mL)
  7. customThe combined extracts were dried
  8. concentrationconcentrated
  9. customThe resulting crude product was purified by column (using amine bound silica gel)

출처 및 근거

ORD 기록
ord-4c52206442894e6eb7f1d14b78b13652
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045486B2

반응 노트

불러오는 중…