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Nitrogen → 3-{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]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 72057
ノート
印刷プレビュー

反応式

HRID 72057 の反応式
[CH3:1][O:2][C:3](=[O:34])[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](=[CH:26][CH:27]=[C:28](Br)[CH:29]=4)[CH:24]=3)=[CH:21][N:22]=2)[CH2:16][C:13]2([CH2:15][CH2:14]2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:35]([O:39][C:40]([N:42]1[CH:47]([C:48]2[NH:49][C:50]([C:53]3[CH:58]=[CH:57][C:56](B4OC(C)(C)C(C)(C)O4)=[CH:55][CH:54]=3)=[CH:51][N:52]=2)[CH:46]2[CH2:68][CH:43]1[CH2:44][CH2:45]2)=[O:41])([CH3:38])([CH3:37])[CH3:36].C([O-])(O)=O.[Na+].N#N>COCCOC.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:35]([O:39][C:40]([N:42]1[CH:47]([C:48]2[NH:49][C:50]([C:53]3[CH:58]=[CH:57][C:56]([C:28]4[CH:27]=[CH:26][C:25]5[C:30](=[CH:31][CH:32]=[C:23]([C:20]6[NH:19][C:18]([CH:17]7[CH2:16][C:13]8([CH2:15][CH2:14]8)[CH2:12][N:11]7[C:9](=[O:10])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:34])[CH:6]([CH3:8])[CH3:7])=[N:22][CH:21]=6)[CH:24]=5)[CH:29]=4)=[CH:55][CH:54]=3)=[CH:51][N:52]=2)[CH:46]2[CH2:68][CH:43]1[CH2:44][CH2:45]2)=[O:41])([CH3:38])([CH3:36])[CH3:37]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 666205563-{5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-2-azabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl esterHCID 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 ester

生成物 1

HCID 66620794
3-{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]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester
収率 56.3%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

A solution of (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 (1.00 g, 1.9 mmol), 3-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (1.31 g, 2.8 mmol) and aq NaHCO3 (7.6 mL of a 1M solution, 7.6 mmol) in DME (20 mL) was degassed with N2 gas for 20 minutes. To the degassed solution was added Pd(PPh3)4 (110 mg, 0.095 mmol) and then the reaction was heated to 80° C. overnight. After cooling to room temperature, the solvent was removed under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic phase was washed with H2O and then brine then dried over sodium sulfate. After filtration the solvent was removed from the filtrate under reduced pressure. The crude material was purified by silica gel chromatography (70-100% EtOAc/Hexanes) to afford 3-{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}-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (835 mg, 1.07 mmol, 56% yield). LCMS-ESI+: calc'd for C46H54N7O5: 784.4 (M+H+). Found: 784.8 (M+H+).

後処理

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed under reduced pressure
  3. dissolutionthe resulting residue was dissolved in ethyl acetate
  4. washThe organic phase was washed with H2O
  5. dry with materialbrine then dried over sodium sulfate
  6. filtrationAfter filtration the solvent
  7. customwas removed from the filtrate under reduced pressure
  8. customThe crude material was purified by silica gel chromatography (70-100% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-671f1c700b90463c97e410f078a3b607
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08822430B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート