Potassium Carbonate → 6-{5-[4-(6-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester

HRID 1185949Notes

Reaction equation

HRID 1185949 reaction equation
COC(=O)NC(C(N1C(C2NC([C:23]3[CH:32]=[CH:31][C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:33]5[CH:38]=[CH:37][C:36]([C:39]6[NH:40][C:41](C7C8CC(CC8)N7C(=O)C(NC(OC)=O)C(C)C)=[N:42][CH:43]=6)=[CH:35][CH:34]=5)[CH:29]=4)[CH:24]=3)=CN=2)CC2(CC2)C1)=O)C(C)C.[CH3:63][O:64][C:65](=[O:104])[NH:66][CH:67]([C:71]([N:73]1[CH:78]([C:79]2[NH:80][C:81](C3C=CC4C(=CC=C(B5OC(C)(C)C(C)(C)O5)C=4)C=3)=[CH:82][N:83]=2)[CH:77]2[CH2:103][CH:74]1[CH2:75][CH2:76]2)=[O:72])[CH:68]([CH3:70])[CH3:69].[C:105]([O:109][C:110]([N:112]1[CH2:118][CH2:117][C:114]2([CH2:116][CH2:115]2)[CH2:113]1)=[O:111])([CH3:108])([CH3:107])[CH3:106].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C>[C:105]([O:109][C:110]([N:112]1[CH:118]([C:41]2[NH:40][C:39]([C:36]3[CH:35]=[CH:34][C:33]([C:28]4[CH:27]=[CH:26][C:25]5[C:30](=[CH:31][CH:32]=[C:23]([C:81]6[NH:80][C:79]([CH:78]7[CH:77]8[CH2:103][CH:74]([CH2:75][CH2:76]8)[N:73]7[C:71](=[O:72])[CH:67]([NH:66][C:65]([O:64][CH3:63])=[O:104])[CH:68]([CH3:69])[CH3:70])=[N:83][CH:82]=6)[CH:24]=5)[CH:29]=4)=[CH:38][CH:37]=3)=[CH:43][N:42]=2)[CH2:117][C:114]2([CH2:116][CH2:115]2)[CH2:113]1)=[O:111])([CH3:108])([CH3:106])[CH3:107]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 66620704[1-(6-{5-[6-(4-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-imidazol-4-yl]-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl esterHCID 66620723[2-Methyl-1-(3-{5-[6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carbonyl)-propyl]carbamic acid methyl esterHCID 69921895HCID 69921895, compound

Product 1

HCID 666207706-{5-[4-(6-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

This compound was prepared using the procedure used to prepare [1-(6-{5-[6-(4-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (example EZ) using [2-Methyl-1-(3-{5-[6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carbonyl)-propyl]-carbamic acid methyl ester (2.25 mmol), 645-(4-Bromo-phenyl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester (2.39 mmol), and potassium carbonate (2M, 4.3 mL, 8.55 mmol). The reaction was performed under an argon atmosphere. The crude reaction was diluted in ethyl acetate, washed with water and purified by normal phase silica chromatography (50-100% Hexanes:EthylAcetate+10% Methanol). 6-{5-[4-(6-{2-[2-(2-Methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester (1.05 g, 60%) was obtained as a tan solid.

Workup

  1. customThis compound was prepared
  2. customThe crude reaction
  3. washwashed with water
  4. custompurified by normal phase silica chromatography (50-100% Hexanes:EthylAcetate+10% Methanol)

Sources & evidence

ORD record
ord-bf3a59d5e8414a0bb246cba264144851
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Reaction notes

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