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

HRID 2169413ノート

反応式

HRID 2169413 の反応式
[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.[Cl: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]([Cl: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

参加物

6

反応物 4

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic 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

生成物 1

HCID 867260449-benzyloxy-6-(5,4'-dichloro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione収率 49.4%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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) (80 mg, 0.155 mmol) in dioxane (3 mL). 4-Chlorophenyl boronic acid (24.248 mg, 0.155 mmol) and a 1N solution of K2CO3 [(64.279 mg, 0.465 mmol) dissolved in 0.7 mL water] were added at room temperature and the reaction was degassed for 30 min under argon. To the reaction mixture, Pd(triphenyl phosphine)4 (17.916 mg, 0.016 mmol) was added, followed by 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (12.729 mg, 0.031 mmol) and the reaction was further degassed for another 10 min. The reaction mixture was heated at 80° C. for 20 min (reaction was monitored by LC-MS). After completion of the reaction, the mixture was filtered and the filtrate was diluted with water (5 mL). After extraction with ethyl acetate (2×20 mL), the organic part was dried over sodium sulphate and concentrated. The resulting crude product was purified by column chromatography (using amine bound silica gel as stationary phase) to get 9-benzyloxy-6-(5,4′-dichloro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (381) (42 mg, 49.39%) as a white solid.

後処理

  1. customIn a sealed tube was placed
  2. customthe reaction was degassed for 30 min under argon
  3. customthe reaction was further degassed for another 10 min
  4. custom(reaction was monitored by LC-MS)
  5. customAfter completion of the reaction
  6. filtrationthe mixture was filtered
  7. additionthe filtrate was diluted with water (5 mL)
  8. extractionAfter extraction with ethyl acetate (2×20 mL)
  9. dry with materialthe organic part was dried over sodium sulphate
  10. concentrationconcentrated
  11. customThe resulting crude product was purified by column chromatography (using amine bound silica gel as stationary phase)

出典と根拠

ORDレコード
ord-b0b20b2eada44d88bef5942d624c5504
出典データセット
uspto-grants-2015_06
特許番号
US09045486B2

反応ノート

読み込み中…