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 71835

Reaction equation

HRID 71835 reaction equation
[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]

Participants

6

Reactant 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

Product 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 esterYield 17.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

(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]+.

Workup

  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)

Sources & evidence

ORD record
ord-4fd4ad4d4e5e45d8a8d6a6e26903ff16
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Linked notes

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