4-tert-Butylcyclohexylamine → HCID 178445671、化合物

HRID 49219

反応式

HRID 49219 の反応式
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]

参加物

5

反応物 2

HCID 793964-tert-Butylcyclohexylamine2 回HCID 179484231-Chloro-4-(2-pyridin-3-yl-ethyl)isoquinoline

生成物 1

HCID 178445671HCID 178445671、化合物

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-47e3e9e69aeb4643984f6cbf68beec1e
出典データセット
uspto-grants-2004_03
特許番号
US06706731B2

関連ノート

読み込み中…