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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
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HRID 528995 반응식
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]
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참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

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

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온도
100 °C

실험 절차

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)−.

후처리

  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)

출처 및 근거

ORD 기록
ord-6c3f243ddccb4445803eed3e837a176d
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09346795B2

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