Triethylamine → N-(3,5-difluorobenzyl)-1-methyl-N-(2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro-[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethyl)cyclohexanecarboxamide

HRID 386610

反応式

HRID 386610 の反応式
[CH3:1][C:2]1([C:8]([OH:10])=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[Cl-].[F:25][C:26]1[CH:27]=[C:28]([CH:51]=[C:52]([F:54])[CH:53]=1)[CH2:29][NH2+:30][CH2:31][C:32]([NH:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[CH2:40][C@@:39]1([C:47](=[O:48])[NH:46][C:45](=[O:49])[N:44]1[CH3:50])[CH2:38]2)=[O:33]>C(Cl)Cl.CN(C=O)C>[F:25][C:26]1[CH:27]=[C:28]([CH:51]=[C:52]([F:54])[CH:53]=1)[CH2:29][N:30]([CH2:31][C:32]([NH:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[CH2:40][C@@:39]1([C:47](=[O:48])[NH:46][C:45](=[O:49])[N:44]1[CH3:50])[CH2:38]2)=[O:33])[C:8]([C:2]1([CH3:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1)=[O:10]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 707441-Methylcyclohexanecarboxylic acidHCID 86647680N-(3,5-difluorobenzyl)-2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethanaminium chloride2 回

生成物 1

HCID 25015785N-(3,5-difluorobenzyl)-1-methyl-N-(2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro-[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethyl)cyclohexanecarboxamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of 1-methylcyclohexanecarboxylic acid (32.0 mg, 0.222 mmol) in DCM (1.5 mL) was added one drop of DMF (cat.), followed by oxalyl chloride (37.0 mg, 0.228 mmol), while at ambient temperature and under a constant stream of nitrogen. Upon cessation of gas evolution, the reaction mixture was cooled to 0° C. prior to the introduction of triethylamine (34.0 mg, 0.333 mmol) as a solution in DCM (2.0 mL), and then N-(3,5-difluorobenzyl)-2-{[(4S)-3-methyl-2,5-dioxo-1′,3′-dihydrospiro[imidazolidine-4,2′-inden]-5′-yl]amino}-2-oxoethanaminium chloride (50.0 mg, 0.111 mmol, Intermediate 1). After 1 hour the reaction mixture was applied directly to a silica gel column for purification, eluting with DCM:MeOH—99:1 to 95:5. Product containing fractions were pooled and concentrated in vacuo to give the title compound. MS: m/z=561 (M+23(Na+)). HRMS: m/z=539.2477; calculated m/z=539.2464 for C29H33N4O4F2.

後処理

  1. customAfter 1 hour the reaction mixture was applied directly to a silica gel column for purification
  2. washeluting with DCM
  3. additionProduct containing fractions
  4. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-b6955718136e40a596cd15ee41e49d7c
出典データセット
uspto-grants-2013_02
特許番号
US08372859B2

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