Sodium Bicarbonate → (1-{2-[5-(6'-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-[2,2'] binaphthalenyl-6-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 79786노트

반응식

HRID 79786 반응식
[CH3:1][O:2][C:3](=[O:32])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[C:26](Br)[CH:27]=3)[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[CH3:33][O:34][C:35](=[O:72])[NH:36][CH:37]([C:41]([N:43]1[CH2:47][CH2:46][CH2:45][CH:44]1[C:48]1[NH:49][C:50]([C:53]2[CH:62]=[CH:61][C:60]3[C:55](=[CH:56][CH:57]=[C:58](B4OC(C)(C)C(C)(C)O4)[CH:59]=3)[CH:54]=2)=[CH:51][N:52]=1)=[O:42])[CH:38]([CH3:40])[CH3:39].C([O-])(O)=O.[Na+]>COCCOC.O>[CH3:1][O:2][C:3](=[O:32])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[CH:27]=[C:26]([C:58]2[CH:57]=[CH:56][C:55]4[C:60](=[CH:61][CH:62]=[C:53]([C:50]5[NH:49][C:48]([CH:44]6[CH2:45][CH2:46][CH2:47][N:43]6[C:41](=[O:42])[CH:37]([NH:36][C:35]([O:34][CH3:33])=[O:72])[CH:38]([CH3:40])[CH3:39])=[N:52][CH:51]=5)[CH:54]=4)[CH:59]=2)[CH:25]=[CH:24]3)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 66620357(1-{2-[5-(6-Bromonaphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterHCID 66620765[2-Methyl-1-(2-{4-[6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester

생성물 1

HCID 66620964(1-{2-[5-(6'-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-[2,2'] binaphthalenyl-6-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester수율 17.1%

시약·촉매·용매 2

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
85 °C

실험 절차

(1-{2-[5-(6-Bromonaphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (0.174 g), [2-Methyl-1-(2-{5-[6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (0.202 g), and NaHCO3 (0.108 g) were dissolved in a mixture of 1,2-dimethoxyethane (6 mL) and water (2 mL). The solution was degassed with nitrogen, and Pd(PPh3)4 (0.0176 g) was added. The reaction mixture was stirred at 85° C. for 16 hours and evaporated under vacuum. Solid was dissolved in ethyl acetate (10 mL) and extracted twice with water (10 mL) and once with brine (10 mL). Solution was evaporated, dissolved in DMF, purified by reverse phase HPLC (5-70% acetonitrile:water), and lyophilized, giving (1-{2-[5-(6′-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-[2,2′]binaphthalenyl-6-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (0.050 g, 16%) as a white solid: 1H-NMR: 300 MHz, (MeOH-d4) δ: 8.3 (m, 4H), 8.1 (m, 6H), 8.0 (s, 2H), 7.8 (d, J=9.4, 2H), 5.3 (m, 2H), 4.3 (d, J=9.0, 2H), 4.1 (m, 2H), 3.9 (m, 2H), 3.7 (s, 6H), 2.6 (m, 2H), 2.2 (m, 6H), 0.9 (m, 12H); MS (ESI) m/z 839 [M+H]+.

후처리

  1. customThe solution was degassed with nitrogen, and Pd(PPh3)4 (0.0176 g)
  2. additionwas added
  3. customevaporated under vacuum
  4. dissolutionSolid was dissolved in ethyl acetate (10 mL)
  5. extractionextracted twice with water (10 mL) and once with brine (10 mL)
  6. customSolution was evaporated
  7. dissolutiondissolved in DMF
  8. custompurified by reverse phase HPLC (5-70% acetonitrile:water)

출처 및 근거

ORD 기록
ord-06103294813440dd89ab86c6afc76c02
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841278B2

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