Potassium Carbonate → 9-benzyloxy-6-(5-chloro-4'-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169417노트

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HRID 2169417 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.[F:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=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:37]2[CH:38]=[CH:39][C:34]([F:33])=[CH:35][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 2856454-Fluorophenylboronic 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 867260499-benzyloxy-6-(5-chloro-4'-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione수율 44.34%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

Into 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) (70 mg, 0.136 mmol) in dioxane (3 mL). 4-Fluorophenyl boronic acid (18.99 mg, 0.14 mmol) and a 1N solution of potassium carbonate [(56.244 mg, 0.407 mmol) in 0.82 mL water] were added at room temperature and the reaction mixture was purged for 30 min with argon. To the reaction Pd(triphenyl phosphine)4 (15.676 mg, 0.014 mmol) was added under argon, followed by 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (11.138 mg, 0.027 mmol). The reaction mixture was further degassed for another 10 min, then heated to 80° C. for 30 min (monitored by LC-MS). The reaction mixture was filtered through a pad of celite. 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 chromatography (using amine bound silica gel) to get 9-benzyloxy-6-(5-chloro-4′-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (385) (32 mg, 44.34%) as an off-white solid.

후처리

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

출처 및 근거

ORD 기록
ord-67e131b208df43f1b78ff61c214f6a6d
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045486B2

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