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 1521526노트

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HRID 1521526 반응식
[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]

참가 물질

6

반응물 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

생성물 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-carboxylate수율 87.8%

시약·촉매·용매 1

HCID 21966342Isopropanol methylene chloride용매

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온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-ac7b7cf27108491e80ed52912f5cf05d
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073931B2

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