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

HRID 2169419ノート

反応式

HRID 2169419 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.[N:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][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:36]2[CH:37]=[CH:38][N:33]=[CH:34][CH:35]=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 2734379(Pyridin-4-yl)boronic 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 867260519-benzyloxy-6-(4-chloro-2-pyridin-4-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione収率 51.1%

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) (100 mg, 0.194 mmol) in dioxane (4 mL). Pyridine 4-boronic acid (23.822 mg, 0.194 mmol), and a 1N solution of potassium carbonate [(80.349 mg, 0.581 mmol) in 0.82 mL water] were added at room temperature and the reaction mixture was purged for 30 min with argon. Pd(triphenyl phosphine)4 (22.395 mg, 0.019 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (15.911 mg, 0.039 mmol) were added to the reaction under argon. The reaction mixture was further degassed for another 10 min and thereafter heated at 80° C. for 4 h (monitored by LC-MS). The reaction mixture was filtered through a pad of celite 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-4-yl-benzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (387) (51 mg, 51.1%) as an off-white solid.

後処理

  1. customIn a sealed tube was placed
  2. customthe reaction mixture was purged for 30 min with argon
  3. customThe reaction mixture was further degassed for another 10 min
  4. filtrationThe reaction mixture was filtered through a pad of celite
  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)

出典と根拠

ORDレコード
ord-2f91a094317440319b1288de7f9add2f
出典データセット
uspto-grants-2015_06
特許番号
US09045486B2

反応ノート

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