Ethyl Acetate → (R)-ethyl 2-(8-(acetoxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate

HRID 1482993ノート

反応式

HRID 1482993 の反応式
[C:1]([O:4][CH2:5][C:6]1[C:7]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:8][C:9]2[N:13]3[CH2:14][CH2:15][NH:16][C@H:17]([CH:18]([CH3:20])[CH3:19])[C:12]3=[N:11][C:10]=2[CH:21]=1)(=[O:3])[CH3:2].Cl[C:27]1[N:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[C:30]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:29][N:28]=1.CCN(C(C)C)C(C)C.CCOC(C)=O>C(Cl)Cl.CC(O)C>[C:1]([O:4][CH2:5][C:6]1[C:7]([S:22]([CH3:25])(=[O:23])=[O:24])=[CH:8][C:9]2[N:13]3[CH2:14][CH2:15][N:16]([C:27]4[N:32]=[C:31]([C:33]([F:35])([F:36])[F:34])[C:30]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:29][N:28]=4)[C@H:17]([CH:18]([CH3:19])[CH3:20])[C:12]3=[N:11][C:10]=2[CH:21]=1)(=[O:3])[CH3:2]

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 2780355Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylateHCID 89816096(R)-(1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methyl acetate

生成物 1

HCID 117935637(R)-ethyl 2-(8-(acetoxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate収率 87.8%

試薬・触媒・溶媒 1

HCID 21966342Isopropanol methylene chloride溶媒

反応条件

温度
80 °C

実験手順

The mixture of (R)-(1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methyl acetate (284 mg, 0.8 mmol), ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate (296 mg, 1.2 mmol, 1.5 eq.) and DIEA (310 mg, 2.4 mmol, 3 eq.) in CH2Cl2/i-PrOH (3 mL/3 mL) was stirred at 80° C. for 16 h. TLC showed compound was consumed completely PE:EtOAc=1:1. The solvents were removed under vacuum and the residue was dissolved in EtOAc (10 mL). Water (10 mL) was added to the mixture. The mixture was extracted with EtOAc (10 mL×3). The organic layers were dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel eluting with PE:EtOAc 5:1 to give (R)-ethyl 2-(8-(acetoxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate (0.41 g, 87% yield) as a pale yellow solid.

後処理

  1. customwas consumed completely PE
  2. customThe solvents were removed under vacuum
  3. dissolutionthe residue was dissolved in EtOAc (10 mL)
  4. additionWater (10 mL) was added to the mixture
  5. extractionThe mixture was extracted with EtOAc (10 mL×3)
  6. dry with materialThe organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by column chromatography on silica gel eluting with PE

出典と根拠

ORDレコード
ord-96f30988f69d42748f0d2fe618d5b584
出典データセット
uspto-grants-2016_08
特許番号
US09416135B2

反応ノート

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