Diisopropylethylamine → 4-chloro-N-({4-chloro-3-[(3-chloro-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

HRID 1875169ノート

反応式

HRID 1875169 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH2:9])=[C:4]([F:10])[C:3]=1[O:11][C:12]1[CH:17]=[C:16]([CH:18]2[CH2:20][CH2:19]2)[CH:15]=[C:14]([Cl:21])[CH:13]=1.[Cl:22][C:23]1[N:24]=[CH:25][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:27]=1[C:28](O)=[O:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.CCOC(C)=O>[Cl:22][C:23]1[N:24]=[CH:25][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:27]=1[C:28]([NH:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:11][C:12]2[CH:17]=[C:16]([CH:18]3[CH2:20][CH2:19]3)[CH:15]=[C:14]([Cl:21])[CH:13]=2)[C:4]=1[F:10])=[O:29]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68485496({4-Chloro-3-[(3-chloro-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)amineHCID 684855334-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid

生成物 1

HCID 684809964-chloro-N-({4-chloro-3-[(3-chloro-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of ({4-chloro-3-[(3-chloro-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)amine (86 mg, 0.264 mmol), 4-chloro-1-({[2(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (73.0 mg, 0.264 mmol) and HATU (100 mg, 0.264 mmol) in DMF (5 ml) was added diisopropylethyl amine (0.092 ml, 0.527 mmol) and the reaction mixture was stirred at rt for 45 minutes. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography to give the desired compound which was only ˜85% pure. This was purified via reverse phase HPLC to give 4-chloro-N-({4-chloro-3-[(3-chloro-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (98 mg, 0.168 mmol, 64% yield).

後処理

  1. washwashed with water
  2. customThe solvent was removed
  3. customthe crude material was purified via silica gel chromatography

出典と根拠

ORDレコード
ord-8a2d840754a94800a9b9d67883b5a7c3
出典データセット
uspto-grants-2012_11
特許番号
US08304419B2

反応ノート

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