4-tert-Butylcyclohexylamine → HCID 178445671, 화합물

HRID 49219

반응식

HRID 49219 반응식
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)=[CH:4][N:3]=1.[C:20]([CH:24]1[CH2:29][CH2:28][CH:27]([NH2:30])[CH2:26][CH2:25]1)([CH3:23])([CH3:22])[CH3:21]>CCOC(C)=O.C([O-])(O)=O.[Na+]>[C:20]([C@H:24]1[CH2:25][CH2:26][C@H:27]([NH:30][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([CH2:12][CH2:13][C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[CH:4][N:3]=2)[CH2:28][CH2:29]1)([CH3:23])([CH3:21])[CH3:22]

참가 물질

5

반응물 2

HCID 793964-tert-Butylcyclohexylamine2회HCID 179484231-Chloro-4-(2-pyridin-3-yl-ethyl)isoquinoline

생성물 1

HCID 178445671HCID 178445671, 화합물

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

실험 절차

Under a N2 atmosphere, 300 mg (1.11 mmol) of 1-chloro-4-[2-(pyridin-3-yl)-ethyl]-isoquinoline (step 1.6) and 520 mg (3.3 mmol) 4-tert-butyl-cyclohexylamine (cis/trans mixture) are stirred at 120° C. After 2 days, a further 520 mg of 4-tert-butyl-cyclohexylamine are added, followed by 1 g after a total of 4 days. Stirring continues for 3 days at 150° C., then the reaction mixture is cooled to RT and diluted with EtOAc and NaHCO3 solution. The water phase is separated off and extracted twice with EtOAc. The organic phases are washed 3 times with water and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2; toluene/EtOAc 3:1) and elution (toluene/EtOAc 3:1+1% Et3N) yields trans 1-(4-tert-butyl-cyclohexylamino)-4-[2-(pyridin-3-yl)-ethyl]-isoquinoline (crystallised from DIPE), followed by cis 1-(4-tert-butyl-cyclohexylamino)-4-[2-(pyridin-3-yl)-ethyl]-isoquinoline. trans derivative: m.p. 124-125° C.; 1H NMR (CDCl3) δ8.47 (m, 2H), 7.83 (d, 1H), 7.77 (m, 2H), 7.64 (t, 1H), 7.47 (m, 2H), 7.19 (m, 1H), 4.98 (d, HN), 4.05 (m, 1H), 3.14 (t, 2H), 2.98 (t, 2H), 2.27 (m, 2H), 1.86 (m, 2H), 1.25 (m, 4H), 1.07 (m, 1H), 0.90 (s, 9H). cis derivative: 1H NMR (CDCl3) δ8.47 (m, 2H), 7.85 (d, 1H), 7.77 (m, 2H), 7.66 (t, 1H), 7.50 (m, 2H), 7.20 (m, 1H), 5.40 (d, HN), 4.45 (m, 1H), 3.14 (t, 2H), 2.98 (t, 2H), 2.13 (m, 2H), 1.7 (m, 4H), 1.28 (m, 2H), 1.13 (m, 1H), 0.92 (s, 9H).

후처리

  1. customafter a total of 4 days
  2. waitcontinues for 3 days at 150° C.
  3. customThe water phase is separated off
  4. extractionextracted twice with EtOAc
  5. washThe organic phases are washed 3 times with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated by evaporation
  8. washColumn chromatography (SiO2; toluene/EtOAc 3:1) and elution (toluene/EtOAc 3:1+1% Et3N)

출처 및 근거

ORD 기록
ord-47e3e9e69aeb4643984f6cbf68beec1e
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06706731B2

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