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Potassium Phosphate, Tribasic → Methyl 4-(4-(dibutylcarbamoyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

HRID 528995
ノート
印刷プレビュー

反応式

HRID 528995 の反応式
CC1(C)COB([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][C:9]=2[C:18]([N:20]2[CH2:29][CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21]2)=[O:19])OC1.Br[C:32]1[N:33]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[CH:34]=[C:35]([C:37]([N:39]([CH2:44][CH2:45][CH2:46][CH3:47])[CH2:40][CH2:41][CH2:42][CH3:43])=[O:38])[N:36]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:40]([N:39]([CH2:44][CH2:45][CH2:46][CH3:47])[C:37]([C:35]1[N:36]=[C:32]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][C:9]=2[C:18]([N:20]2[CH2:29][CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21]2)=[O:19])[N:33]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[CH:34]=1)=[O:38])[CH2:41][CH2:42][CH3:43]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 71060775Methyl 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoateHCID 710622212-Bromo-N,N-dibutyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxamide

生成物 1

HCID 71062252Methyl 4-(4-(dibutylcarbamoyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate収率 58.9%

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of methyl 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (2.0 g, 5.05 mmol) in dioxane (40 mL) was added Pd(dppf)2Cl2 (77 mg, 0.10 mmol), 2-bromo-N,N-dibutyl-1-((2-(trimethylsilyl) ethoxy)methyl)-1H-imidazole-4-carboxamide (910 mg, 2.10 mmol) and K3PO4 (1.34 g, 6.31 mmol). The reaction mixture was degassed for 30 min, heated at 100° C. for 16 h and concentrated in vacuo. The resulting residue was dissolved in EtOAc and washed with water, dried over Na2SO4, and concentrated to give the crude product. The crude material was purified by flash chromatography (gradient from 0% to 80%, EtOAc/hexanes) to provide the title compound (800 mg, 57%). 1H NMR (CD3OD, 1:1 mixture of amide rotamers) δ 8.23 (dd, J=6.4, 1.6 Hz, 1H), 8.13-8.12 (m, 1H), 7.98 (dd, J=14.4, 8.0 Hz, 1H), 7.78 (s, 0.5H), 7.67 (s, 0.5H), 7.24-7.12 (m, 3.5H), 6.93 (d, J=7.2 Hz, 0.5H), 5.39 (s, 1H), 5.30 (s, 1H), 4.85-4.75 (m, 2H), 4.58-4.35 (m, 1H), 3.99 (s, 3H), 3.71-3.62 (m, 3H), 3.56 (t, J=6.0 Hz, 2H), 3.45-3.36 (m, 2H), 2.90-2.80 (m, 2H), 1.65-1.31 (m, 8H), 1.00-0.91 (m, 5H), 0.80-0.73 (m, 3H), 0.04 (s, 4.5H), 0.02 (s, 4.5H); MS (ESI−) m/z 646.2 (M−H)−.

後処理

  1. customThe reaction mixture was degassed for 30 min
  2. concentrationconcentrated in vacuo
  3. dissolutionThe resulting residue was dissolved in EtOAc
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give the crude product
  8. customThe crude material was purified by flash chromatography (gradient from 0% to 80%, EtOAc/hexanes)

出典と根拠

ORDレコード
ord-6c3f243ddccb4445803eed3e837a176d
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09346795B2

反応ノート

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