Potassium Carbonate → [1-(2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-4-methylene pyrrolidin-2-yl]-3H-imidazol-4-yl]-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 72043

Reaction equation

[CH3:1][O:2][C:3](=[O:62])[NH:4][CH:5]([C:9]([N:11]1[CH:17]([C:18]2[NH:19][C:20]([C:23]3[CH:32]=[CH:31][C:30]4[C:25](=CC=[C:28]([C:33]5[CH:38]=[CH:37][C:36]([C:39]6[NH:40][C:41]([CH:44]7[CH:49]8[CH2:50][CH:46](CC8)[N:45]7[C:51](=[O:61])[CH:52]([NH:56][C:57]([O:59][CH3:60])=[O:58])[CH:53]([CH3:55])[CH3:54])=[N:42][CH:43]=6)=[CH:35][CH:34]=5)[CH:29]=4)[CH:24]=3)=[CH:21][N:22]=2)[CH2:16][C:13]2(C[CH2:14]2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].COC(=O)N[CH:67](C(N1CCCC1C1NC(C2C=CC3C(=CC=C(B4OC(C)(C)C(C)(C)O4)C=3)C=2)=CN=1)=O)[CH:68](C)C.COC(=O)NC(C(N1CC(=C)CC1C1NC(C2C=CC(Br)=CC=2)=CN=1)=O)C(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[K+].[K+]>>[CH3:60][O:59][C:57](=[O:58])[NH:56][CH:52]([C:51]([N:45]1[CH2:46][CH2:50][CH2:49][CH:44]1[C:41]1[NH:40][C:39]([C:36]2[CH:35]=[CH:34][C:33]3[C:38](=[CH:67][CH:68]=[C:29]([C:30]4[CH:25]=[CH:24][C:23]([C:20]5[NH:19][C:18]([CH:17]6[CH2:16][C:13](=[CH2:14])[CH2:12][N:11]6[C:9](=[O:10])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:62])[CH:6]([CH3:8])[CH3:7])=[N:22][CH:21]=5)=[CH:32][CH:31]=4)[CH:28]=3)[CH:37]=2)=[CH:43][N:42]=1)=[O:61])[CH:53]([CH3:54])[CH3:55]

Participants

Reactant 5

HCID 11430Potassium Carbonate

HCID 62657Potassium Phosphate, Tribasic

HCID 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 ester

HCID 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

HCID 66621522(1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-methylene-pyrrolidine-1-carbonyl]-2-methyl-propyl)-carbamic acid methyl ester

Product 1

HCID 66620671[1-(2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-4-methylene pyrrolidin-2-yl]-3H-imidazol-4-yl]-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl esterYield 5%

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 using [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 (0.177 g, 0.324 mmol) and (1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-methylene-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (0.100 g, 0.216 mmol). Potassium phosphate (aqueous, 0.32 mL, 0.648 mmol) was substituted for potassium carbonate and the reaction was performed under an argon atmosphere. The crude reaction was purified by reverse phase HPLC (10-45% acetonitrile:water; 0.1% formic acid modifier), and lyophilized giving [1-(2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-4-methylene pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (0.009 g, 5%) as a white solid.

Workup

customThis compound was prepared
customThe crude reaction
customwas purified by reverse phase HPLC (10-45% acetonitrile:water; 0.1% formic acid modifier)

Sources & evidence

ORD record: ord-45a0b722fe4a4b848399e7c33669692e
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822430B2

Linked notes

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