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

HRID 1173160노트

반응식

HRID 1173160 반응식
[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>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]

참가 물질

6

반응물 4

HCID 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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 W-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 [4+H]+ 546.3, obs'd 546.2.

후처리

  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)

출처 및 근거

ORD 기록
ord-9a6c0a94bd72414e9769294986d68762
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834026B2

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