Pyridine → (R)-2-Methyl-4-(3-trifluoromethyl-2-pyridyl)-N-(1-methyl-1,2,3,4-tetrahydro-quinolin-7-yl) piperazine-1-carboxamide

HRID 494227노트

반응식

HRID 494227 반응식
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][N:9]2[CH3:12])=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl[C:20](OC1C=CC=CC=1)=[O:21].C(N(CC)CC)C.[CH3:36][C@@H:37]1[CH2:42][N:41]([C:43]2[C:48]([C:49]([F:52])([F:51])[F:50])=[CH:47][CH:46]=[CH:45][N:44]=2)[CH2:40][CH2:39][NH:38]1>C(Cl)Cl>[CH3:36][C@@H:37]1[CH2:42][N:41]([C:43]2[C:48]([C:49]([F:52])([F:50])[F:51])=[CH:47][CH:46]=[CH:45][N:44]=2)[CH2:40][CH2:39][N:38]1[C:20]([NH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][N:9]2[CH3:12])=[CH:4][CH:3]=1)=[O:21]

참가 물질

7

반응물 5

HCID 1049PyridineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 112174211-Methyl-1,2,3,4-tetrahydroquinolin-7-amineHCID 11528875(R)-3-Methyl-1-(3-(trifluoromethyl)pyridin-2-yl)piperazine

생성물 1

HCID 57682689(R)-2-Methyl-4-(3-trifluoromethyl-2-pyridyl)-N-(1-methyl-1,2,3,4-tetrahydro-quinolin-7-yl) piperazine-1-carboxamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 7-amino-1-methyl-1,2,3,4-tetrahydroquinoline (D3) (300 mg, 1.85 mmol) in DCM (5 ml) was added pyridine (164 ul, 2 mmol) followed by phenyl chloroformate (255 ul, 2 mmol) and the solution stirred at ambient temperature for 50 mins. Triethylamine (516 μl 3.7 mmol) was then added followed by a solution of (R)-2-methyl-4-(3-trifluoromethyl-2-pyridyl)piperazine (D22) (454 mg, 1.85 mmol) in DCM (5 ml) and the reaction stirred at ambient temperature until complete by tlc. The reaction mixture was washed (1M HCl, brine), dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by flash chromatography, eluting with an EtOAc/40-60° C. petroleum ether gradient, to give the title compound as a white solid. 1H NMR (250 MHz, CDCl3) δ (ppm): 8.47 (dd, 1H), 7.90 (dd, 1H), 7.05 (dd, 1H), 6.84 (d, 1H), 6.78 (d, 1H), 6.49 (dd, 1H), 6.25 (br, 1H), 4.34 (m, 1H), 3.86 (m, 1H), 3.17-3.62 (m, 6H), 3.05 (m, 1H), 2.89 (s, 3H), 2.70.(t, 2H), 1.96 (m, 2H), 1.36 (d, 3H). MS (ES): MH+ 434.

후처리

  1. stirringthe reaction stirred at ambient temperature until complete by tlc
  2. washThe reaction mixture was washed (1M HCl, brine)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customto give the crude product which
  6. customwas purified by flash chromatography
  7. washeluting with an EtOAc/40-60° C. petroleum ether gradient

출처 및 근거

ORD 기록
ord-f0c3c9c527be42f9baf232a948d117a0
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07538121B2

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