Diisopropylethylamine → Tert-butyl 4-(4-(1-(4-hydroxyphenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate

HRID 1618337노트

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HRID 1618337 반응식
Cl[C:2]1[N:7]=[C:6]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH:14][C:15]2[CH:27]=[CH:26][C:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:17][CH:16]=2)[N:3]=1.[NH2:28][C:29]1([C:32]2[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=2)[CH2:31][CH2:30]1.CCN(C(C)C)C(C)C>C1COCC1.C(Cl)Cl>[OH:38][C:35]1[CH:34]=[CH:33][C:32]([C:29]2([NH:28][C:2]3[N:7]=[C:6]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH:14][C:15]4[CH:27]=[CH:26][C:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:17][CH:16]=4)[N:3]=3)[CH2:30][CH2:31]2)=[CH:37][CH:36]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 211210144-(1-Aminocyclopropyl)phenolHCID 86652471Tert-butyl 4-(4-chloro-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate

생성물 1

HCID 67284923Tert-butyl 4-(4-(1-(4-hydroxyphenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate수율 78.2%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

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온도
65 °C

실험 절차

To a solution of tert-butyl 4-(4-chloro-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate (2 g, 4.94 mmol) in THF (30 mL) was added 4-(1-aminocyclopropyl)phenol (0.811 g, 5.44 mmol) and Hunig's Base (3.45 mL, 19.76 mmol). The resulting mixture was stirred for 16 h. The reaction was then warmed to 65° C. for 2 h at which point the reaction became a homogeneous solution. The reaction was cooled and diluted with DCM and washed with water and brine. The organic layer was collected, dried over sodium sulfate, and concentrated under vacuum to give an oily residue. The residue was purified by silica gel chromatography using 20-40% EtOAc/Hexanes to give tert-butyl 4-(4-(1-(4-hydroxyphenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate (2 g). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.30-1.37 (m, 4H), 1.60 (s, 9H), 4.67-4.77 (m, 2H), 4.85 (br. s., 1H), 6.04 (br. s., 1H), 6.70-6.81 (m, 2H), 7.11-7.22 (m, 2H), 7.47-7.66 (m, 2H), 7.79-8.01 (m, 2H); LC-MS (Condition A), MS m/z (M++H) 518.0.

후처리

  1. temperatureThe reaction was cooled
  2. washwashed with water and brine
  3. customThe organic layer was collected
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customto give an oily residue
  7. customThe residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-ae0809ef141241d18233f344e04222ff
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765944B2

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