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

HRID 1185889
ノート
印刷プレビュー

反応式

HRID 1185889 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]#[N:14])[CH2:10][CH:9]1[C:15]1[NH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23](B3OC(C)(C)C(C)(C)O3)=[CH:22][CH:21]=2)=[CH:18][N:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:35][O:36][C:37](=[O:68])[NH:38][CH:39]([C:43]([N:45]1[CH:51]([C:52]2[NH:53][C:54]([C:57]3[CH:66]=[CH:65][C:64]4[C:59](=[CH:60][CH:61]=[C:62](Br)[CH:63]=4)[CH:58]=3)=[CH:55][N:56]=2)[CH2:50][C:47]2([CH2:49][CH2:48]2)[CH2:46]1)=[O:44])[CH:40]([CH3:42])[CH3:41].C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]#[N:14])[CH2:10][CH:9]1[C:15]1[NH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:62]3[CH:61]=[CH:60][C:59]4[C:64](=[CH:65][CH:66]=[C:57]([C:54]5[NH:53][C:52]([CH:51]6[CH2:50][C:47]7([CH2:48][CH2:49]7)[CH2:46][N:45]6[C:43](=[O:44])[CH:39]([NH:38][C:37]([O:36][CH3:35])=[O:68])[CH:40]([CH3:42])[CH3:41])=[N:56][CH:55]=5)[CH:58]=4)[CH:63]=3)=[CH:22][CH:21]=2)=[CH:18][N:19]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 66620764(1-{6-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterHCID 666208224-Cyano-2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 66620944
4-Cyano-2-{5-[4-(6-(2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester
収率 68.4%

試薬・触媒・溶媒 1

HCID 178418397HCID 178418397、化合物触媒

実験手順

4-Cyano-2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.990 g, 2.13 mmol), (1-{6-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1.007 g, 1.92 mmol), Pd(PPh3)4 (222 mg, 0.192 mmol) and K2CO3 (2.0 M in H2O, 2.1 mL, 4.2 mmol) were combined in 1,2-dimethoxymethane. The mixture was degassed for 10 min with bubbling N2 then heated to reflux for 4 h then cooled. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine before being dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (EtOAc, then 2% MeOH/DCM, then 4% MeOH/DCM) to provide the title compound (1.028 g, 68%).

後処理

  1. customThe mixture was degassed for 10 min with bubbling N2
  2. temperaturethen heated
  3. temperatureto reflux for 4 h
  4. temperaturethen cooled
  5. additionThe reaction mixture was diluted with EtOAc
  6. washwashed with saturated aqueous NaHCO3 and brine
  7. dry with materialbefore being dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified by silica column chromatography (EtOAc

出典と根拠

ORDレコード
ord-51fd64fa19df478e9f6208740f6a5172
出典データセット
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08669234B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート