Triethylamine → (R)-tert-butyl-(2-(3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-5-(4-(4,4,5,5,5-pentafluoropentyl)-piperazin-1-yl)-2,3-dihydropyrimidin-1(6H)-yl)-1-phenylethyl)carbamate

HRID 574272노트

반응식

HRID 574272 반응식
[F:1][C:2]([F:11])([C:7]([F:10])([F:9])[F:8])[CH2:3][CH2:4][CH2:5]O.C(N(CC)CC)C.CS(Cl)(=O)=O.[F:24][C:25]1[CH:62]=[CH:61][CH:60]=[C:59]([C:63]([F:66])([F:65])[F:64])[C:26]=1[CH2:27][N:28]1[C:33]([CH3:34])=[C:32]([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[C:31](=[O:41])[N:30]([CH2:42][C@H:43]([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:29]1=[O:58].C(=O)([O-])[O-].[K+].[K+]>ClCCl.C(#N)C>[C:53]([O:52][C:51](=[O:57])[NH:50][C@H:43]([C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[CH2:42][N:30]1[C:31](=[O:41])[C:32]([N:35]2[CH2:36][CH2:37][N:38]([CH2:5][CH2:4][CH2:3][C:2]([F:11])([F:1])[C:7]([F:10])([F:9])[F:8])[CH2:39][CH2:40]2)=[C:33]([CH3:34])[N:28]([CH2:27][C:26]2[C:59]([C:63]([F:65])([F:66])[F:64])=[CH:60][CH:61]=[CH:62][C:25]=2[F:24])[C:29]1=[O:58])([CH3:54])([CH3:55])[CH3:56]

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 5479674,4,5,5,5-Pentafluoropentan-1-olHCID 53238962(R)-tert-butyl (2-(3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-5-(piperazin-1-yl)-2,3-dihydropyrimidin-1(6H)-yl)-1-phenylethyl)carbamate

생성물 1

HCID 88885349(R)-tert-butyl-(2-(3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-5-(4-(4,4,5,5,5-pentafluoropentyl)-piperazin-1-yl)-2,3-dihydropyrimidin-1(6H)-yl)-1-phenylethyl)carbamate수율 21.3%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

To a solution of 100 μl (0.416 mmol) of 4,4,5,5,5-pentafluoropentan-1-ol in 2 mL of dichloromethane were added 69 μl (1.2 eq) of triethylamine and 36 μl (1.1 eq) of methanesulfonyl chloride in the order, followed by stirring at room temperature for 30 min. The solution was washed with an aqueous saturated sodium bicarbonate solution, dried over sodium sulfate, filtrated and concentrated to produce a colorless oil. 60 μl of the oil, 30 mg of (R)-tert-butyl (2-(3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-5-(piperazin-1-yl)-2,3-dihydropyrimidin-1(6H)-yl)-1-phenylethyl)carbamate (0.049 mmol), and 21 mg (0.149 mmol) of potassium carbonate were dissolved at 80° C. for 7 hrs in 2 mL of acetonitrile, with stirring. The solution was concentrated, diluted with dichloromethane, and washed with an aqueous saturated sodium bicarbonate solution. After concentration of the organic layer thus formed, the residue was purified by prep-TLC (eluent: hexane/ethyl acetate, 1/1) and dried in a vacuum to afford 8 mg of the compound as a colorless oil (yield 21%). 1H NMR (300 MHz, CDCl3) δ 1.36 (9H, s), 1.77 (2H, m), 2.14 (4H, m), 2.36 (3H, s), 2.42 (2H, m), 2.53 (2H, m), 2.75 (2H, m), 3.61 (2H, m), 4.05 (1H, m), 4.28 (1H, m), 5.01 (1H, m), 5.33 (1H, m), 5.51 (1H, m), 5.82 (1H, d), 7.19-7.44 (7H, m), 7.55 (1H, m)

후처리

  1. washThe solution was washed with an aqueous saturated sodium bicarbonate solution
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltrated
  4. concentrationconcentrated
  5. customto produce a colorless oil
  6. stirringwith stirring
  7. concentrationThe solution was concentrated
  8. additiondiluted with dichloromethane
  9. washwashed with an aqueous saturated sodium bicarbonate solution
  10. customAfter concentration of the organic layer thus formed
  11. customthe residue was purified by prep-TLC (eluent: hexane/ethyl acetate, 1/1)
  12. customdried in a vacuum

출처 및 근거

ORD 기록
ord-3a8f27860de14b849507b0b57d1766ce
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034850B2

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