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 2169417ノート

反応式

HRID 2169417 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.[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

参加物

6

反応物 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

生成物 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-dione収率 44.34%

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

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.

後処理

  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)

出典と根拠

ORDレコード
ord-67e131b208df43f1b78ff61c214f6a6d
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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