Diisopropylethylamine → trans-(4-Cyclobutylpiperazin-1-yl)-[2-(6-(trifluoromethyl)pyridin-3-yl)cyclopropyl]methanone

HRID 572020노트

반응식

HRID 572020 반응식
[F:1][C:2]([F:16])([F:15])[C:3]1[N:8]=[CH:7][C:6]([C@@H:9]2[CH2:11][C@H:10]2[C:12]([OH:14])=O)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.Cl.[CH:50]1([N:54]2[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)[CH2:53][CH2:52][CH2:51]1>CN(C=O)C.CCOC(C)=O.CCCCCC>[CH:50]1([N:54]2[CH2:59][CH2:58][N:57]([C:12]([C@@H:10]3[CH2:11][C@H:9]3[C:6]3[CH:7]=[N:8][C:3]([C:2]([F:1])([F:16])[F:15])=[CH:4][CH:5]=3)=[O:14])[CH2:56][CH2:55]2)[CH2:53][CH2:52][CH2:51]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 451567991-Cyclobutylpiperazine dihydrochlorideHCID 66689840trans-2-[6-(Trifluoromethyl)pyridin-3-yl]cyclopropanecarboxylic acid

생성물 1

HCID 25196792trans-(4-Cyclobutylpiperazin-1-yl)-[2-(6-(trifluoromethyl)pyridin-3-yl)cyclopropyl]methanone수율 36%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 21226206Ethyl acetate hexane용매

실험 절차

To a stirring solution of 26C (16 mg, 0.070 mmol) in DMF (0.5 mL) at ambient temperature was added DIPEA (0.050 mL, 0.28 mmol) and TBTU (23 mg, 0.070 mmol). After stirring for 2 min, 4A (16 mg, 0.08 mmol) was added in one portion. After stirring for 19 h, the reaction was concentrated under reduced pressure. The residue was diluted with EtOAc (15 mL) then washed successively with dilute aq. K2CO3 (5 mL), H2O (2 mL), and brine (3 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The resulting residue was subjected to flash chromatography (basic alumina-8 g; gradient elution: 5% EtOAc/Hexane for 1 min then 5-100% EtOAc/Hexane over 13 min at 18 mL/min) to afford 8.7 mg 26D (36% yield). m/z (ES+) M+1=285.2; HPLC tR=0.75 min. 1H NMR (500 MHz, CDCl3) δ 8.53 (dd, J=2.1, 0.6 Hz, 1H), 7.59 (d, J=8.2 Hz, 1H), 7.55 (dd, J=8.2, 2.1 Hz, 1H), 3.69-3.59 (m, 4H), 2.74 (quintet, J=7.9 Hz, 1H), 2.60 (ddd, J=9.0, 6.3, 4.0 Hz, 1H), 2.36-2.29 (m, 4H), 2.05 (m, 3H), 1.93-1.82 (m, 2H), 1.79-1.66 (m, 3H), 1.35 (ddd, J=8.7, 6.3, 4.6 Hz, 1H).

후처리

  1. stirringAfter stirring for 19 h
  2. concentrationthe reaction was concentrated under reduced pressure
  3. additionThe residue was diluted with EtOAc (15 mL)
  4. washthen washed successively with dilute aq. K2CO3 (5 mL), H2O (2 mL), and brine (3 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. washgradient elution
  9. wait5% EtOAc/Hexane for 1 min

출처 및 근거

ORD 기록
ord-7fd20183032a4f4eb4435d7d2b384c7c
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029381B2

반응 노트

불러오는 중…