Diisopropylethylamine → (R)-methyl-2-(5-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

HRID 1482986노트

반응식

HRID 1482986 반응식
[CH3:1][O:2][C:3]([C:5]1[C:6]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:7][C:8]2[N:12]3[CH2:13][CH2:14][NH:15][C@H:16]([CH:17]([CH3:19])[CH3:18])[C:11]3=[N:10][C:9]=2[CH:20]=1)=[O:4].Cl[C:26]1[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:29]([C:36]([OH:39])([CH3:38])[CH3:37])=[CH:28][N:27]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[C:6]([S:21]([CH3:24])(=[O:22])=[O:23])=[CH:7][C:8]2[N:12]3[CH2:13][CH2:14][N:15]([C:26]4[N:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[C:29]([C:36]([OH:39])([CH3:37])[CH3:38])=[CH:28][N:27]=4)[C@H:16]([CH:17]([CH3:19])[CH3:18])[C:11]3=[N:10][C:9]=2[CH:20]=1)=[O:4]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 898155822-(2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl)propan-2-olHCID 89815671(R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

생성물 1

HCID 89816015(R)-methyl-2-(5-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate수율 62%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
165 °C

실험 절차

(R)-methyl-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (224 mg, 0.639 mmol) and 2-(2-chloro-4-(trifluoromethyl)pyrimidin-5-yl)propan-2-ol (192 mg, 0.799 mmol) were combined in a small vial and azeotroped with benzene to remove any residual water. A mixture of dioxane (1 mL) and iPr2NEt (0.22 mL, 1.28 mmol) was degassed with N2 for 10 minutes. This mixture was then added to the reaction vial and sealed with a Teflon® coated cap which was then wrapped with Teflon® tape. The resulting suspension was then placed in a 165° C. silicone oil bath at which point the mixture became homogeneous. The resulting solution stirred at 165° C. for 21 h. After the solvents were removed by rotovap, the mixture was purified using ISCO FCC, eluting with 50% EtOAc in Hexanes to obtain 219 mg of (R)-methyl-2-(5-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate as a white solid (62% yield, 40% ee).

후처리

  1. customazeotroped with benzene
  2. customto remove any residual water
  3. customwas degassed with N2 for 10 minutes
  4. additionThis mixture was then added to the reaction vial
  5. customsealed with a Teflon®
  6. customcoated cap which
  7. customwas then placed in a 165° C.
  8. customAfter the solvents were removed by rotovap
  9. customthe mixture was purified
  10. washeluting with 50% EtOAc in Hexanes

출처 및 근거

ORD 기록
ord-fd42156e1b174b5f86e6742fbcfa89a9
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09416135B2

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