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 2392490

반응식

HRID 2392490 반응식
[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]

참가 물질

6

반응물 5

HCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 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 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 esterHCID 66621522(1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-methylene-pyrrolidine-1-carbonyl]-2-methyl-propyl)-carbamic acid methyl ester

생성물 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 ester수율 5%

실험 절차

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. 1H NMR (400 MHz, CDCl3) δ 8.12-7.96 (m, 1H), 7.93-7.79 (m, 5H), 7.77-7.67 (m, 5H), 6.32 (s, 1H), 5.73-5.54 (m, 1H), 5.50-5.22 (m, 6H), 4.49-4.28 (m, 3H), 3.96-3.82 (m, 2H), 3.72 (s, 9H), 3.06-2.86 (m, 2H), 2.50-2.34 (m, 1H), 2.31-2.21 (m, 1H), 2.18-2.09 (m, 2H), 2.05-1.95 (m, 3H), 1.90 (s, 4H), 1.26 (s, 3H), 1.13-1.04 (m, 3H).

후처리

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

출처 및 근거

ORD 기록
ord-03ceb59a27e44c34819bc629b5b4ce30
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08273341B2

연결된 노트

불러오는 중…