Triethylamine → 1-[4-(6-Chloroquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one

HRID 1772207노트

반응식

HRID 1772207 반응식
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:16][CH2:15][CH:14]([O:17][CH2:18][C:19](O)=[O:20])[CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:22]([F:25])([F:24])[F:23])([O-:3])=[O:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[NH2:55][CH2:56][CH2:57][N:58]([CH2:70][CH2:71]Cl)[C:59]1[CH:68]=[CH:67][C:66]2[C:61](=[CH:62][CH:63]=[C:64]([Cl:69])[CH:65]=2)[N:60]=1>ClCCl>[Cl:69][C:64]1[CH:65]=[C:66]2[C:61](=[CH:62][CH:63]=1)[N:60]=[C:59]([N:58]1[CH2:70][CH2:71][N:55]([C:19](=[O:20])[CH2:18][O:17][CH:14]3[CH2:13][CH2:12][CH:11]([NH:10][C:7]4[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:22]([F:23])([F:24])[F:25])[CH:6]=4)[CH2:16][CH2:15]3)[CH2:56][CH2:57]1)[CH:68]=[CH:67]2

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acidHCID 86719468N-(2-aminoethyl)-6-chloro-N-(2-chloroethyl)quinolin-2-amine

생성물 1

HCID 747667761-[4-(6-Chloroquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one수율 42.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 2-[(4-[4-nitro-3-(trifluoromethyl)phenyl]aminocyclohexyl)oxy]acetic acid (100 mg, 0.28 mmol) in dichloromethane (20 ml) was added EDAC.HCl (79.4 mg, 0.41 mmol, 1.5 eq), HOBt (56 mg, 0.41 mmol, 1.5 eq), triethylamine (111.6 mg, 1.10 mmol, 4 eq), and N-(2-aminoethyl)-6-chloro-N-(2-chloroethyl)quinolin-2-amine (93.8 mg, 0.33 mmol, 1.2 eq). The resulting solution was stirred overnight at room temperature and then quenched by the addition of water (50 ml), extracted with dichloromethane (3×30 ml). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue. The crude material was purified by Pre-TLC using 4% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 1-[4-(6-chloroquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one as a yellow solid (69.8 mg, 42%). (ES, m/z): [M+H]+ 592.35; 1H NMR (300 MHz, CDCl3): δ 8.00 (d, J=9.0 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.61 (s, 2H), 7.52 (s, 1H), 7.01 (d, J=9.0 Hz, 1H), 6.91 (s, 1H), 6.84 (d, J=2.4 Hz, 1H), 6.61-6.65 (m, 1H), 4.45 (d, J=7.5 Hz, 1H), 4.26 (s, 2H), 3.75-3.78 (m, 7H), 3.37-3.50 (m, 2H), 2.14 (d, J=10.5 Hz, 4H), 1.44-1.51 (m, 2H), 1.24-1.35 (m, 2H).

후처리

  1. customquenched by the addition of water (50 ml)
  2. extractionextracted with dichloromethane (3×30 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto give a residue
  7. customThe crude material was purified by Pre-TLC
  8. washto elute
  9. concentrationconcentrated under vacuum

출처 및 근거

ORD 기록
ord-172bdb5d9f17404fb878ee1953364445
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249102B2

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