Carbonate Ion → N-(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)-7-benzyl-2,7-diazaspiro[4.4]nonane-2-carboxamide

HRID 1984782ノート

反応式

HRID 1984782 の反応式
[N:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)=[C:2]=[O:3].[CH2:13]([N:20]1[CH2:24][CH2:23][C:22]2([CH2:28][CH2:27][NH:26][CH2:25]2)[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[NH2:29][C:30]1[CH:31]=[C:32]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH:33]=[CH:34][C:35]=1[NH:36]C(=O)OC(C)(C)C.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-]>ClCCl>[NH2:36][C:35]1[CH:34]=[CH:33][C:32]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:31][C:30]=1[NH:29][C:8]([C:7]1[CH:11]=[CH:12][C:4]([NH:1][C:2]([N:26]2[CH2:27][CH2:28][C:22]3([CH2:23][CH2:24][N:20]([CH2:13][C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH2:21]3)[CH2:25]2)=[O:3])=[CH:5][CH:6]=1)=[O:9]

参加物

7

反応物 5

HCID 19660Carbonate IonHCID 81531DiisopropylethylamineHCID 27333234-Isocyanatobenzoyl chlorideHCID 426145422-Benzyl-2,7-diazaspiro[4.4]nonaneHCID 57717454N-(3-Amino[1,1'-biphenyl]-4-yl)-carbamic Acid tert-Butyl Ester

生成物 1

HCID 24746278N-(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)-7-benzyl-2,7-diazaspiro[4.4]nonane-2-carboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of stirring 4-isocyanatobenzoyl chloride (50 mg, 0.275 mmol) in 3 mL of dichloromethane was added 2-benzyl-2,7-diazaspiro[4,4]nonane (60 mg, 0.275 mmol) slowly over a period of 10 minutes. The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl (3-aminobiphenyl-4-yl)carbamate (78.2 mg, 0.275 mmol) was then added, followed by the addition of diisopropylethylamine (48 μL, 0.275 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. Argonaut MP-Carbonate scavenging resin (285 mg, 0.825 mmol) was then added and stirred overnight at room temperature. The mixture was then filtered from scavenging resin and concentrated. Added dichloromethane (1 mL) and stirred, then treated with trifluoroacetic acid (1 mL). The reaction mixture was concentrated after 2 hours of stirring at room temperature and the crude residue was purified by reverse-phase chromatography (5-50-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+546.3, obs'd 546.2.

後処理

  1. stirringto stir for 1 hour at room temperature
  2. stirringstirred overnight at room temperature
  3. filtrationThe mixture was then filtered
  4. concentrationconcentrated
  5. stirringAdded dichloromethane (1 mL) and stirred
  6. additiontreated with trifluoroacetic acid (1 mL)
  7. concentrationThe reaction mixture was concentrated after 2 hours
  8. stirringof stirring at room temperature
  9. customthe crude residue was purified by reverse-phase chromatography (5-50-95% acetonitrile/water with 0.1% formic acid)

出典と根拠

ORDレコード
ord-b5047b35790242088743becb478e8112
出典データセット
uspto-grants-2009_06
特許番号
US07544695B2

反応ノート

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