Trifluoroacetic acid → N-(2-amino-5-phenylphenyl)-4-{1,8-diazaspiro[4.5]decan-8-ylcarbonyl}benzamide

HRID 1984781Notes

Reaction equation

HRID 1984781 reaction equation
[C:1](Cl)(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[NH2:13][C:14]1[CH:15]=[C:16]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:17]=[CH:18][C:19]=1[NH:20]C(=O)OC(C)(C)C.C(N(C(C)C)CC)(C)C.[N:43]1(C(OC(C)(C)C)=O)[C:47]2([CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[CH2:46][CH2:45][CH2:44]1.C(=O)([O-])[O-].FC(F)(F)C(O)=O>ClCCl.CN(C)C=O>[NH2:20][C:19]1[CH:18]=[CH:17][C:16]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:15][C:14]=1[NH:13][C:1](=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:50]2[CH2:51][CH2:52][C:47]3([NH:43][CH2:44][CH2:45][CH2:46]3)[CH2:48][CH2:49]2)=[O:7])=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 7488Terephthaloyl chlorideHCID 19660Carbonate IonHCID 81531Diisopropylethylamine2×HCID 34178602tert-Butyl 1,8-diazaspiro(4.5)decane-1-carboxylateHCID 57717454N-(3-Amino[1,1'-biphenyl]-4-yl)-carbamic Acid tert-Butyl Ester

Product 1

HCID 25218563N-(2-amino-5-phenylphenyl)-4-{1,8-diazaspiro[4.5]decan-8-ylcarbonyl}benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of stirring terephthaloyl chloride (50 mg, 0.246 mmol) in 3 mL dichloromethane was added tert-butyl (3-aminobiphenyl-4-yl)carbamate (70 mg, 0.246 mmol) slowly over a period of 10 minutes, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 30 min. at room temperature. Tert-butyl 1,8-diazaspiro[4,5]decane-1-carboxylate (59 mg, 0.246 mmol) was then added, followed by the addition of diisopropylethylamine (43 μL, 0.246 mmol). The reaction mixture was allowed to stir for 1 hour at room temperature. The reaction mixture became cloudy. Argonaut MP-Carbonate scavenging resin (255 mg, 0.738 mmol) was then added and stirred overnight at room temperature. The mixture was then fully dissolved by adding 3 mL dimethylformamide, filtered from scavenging resin, and concentrated. Added dichloromethane (1 mL) and stirred to form suspension, 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 (5-75-95% acetonitrile/water with 0.1% formic acid). The appropriate fractions were combined and lyophilized. MS (ESI+): cal'd [M+H]+ 455.2, obs'd 455.1.

Workup

  1. stirringto stir for 1 hour at room temperature
  2. stirringstirred overnight at room temperature
  3. dissolutionThe mixture was then fully dissolved
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringAdded dichloromethane (1 mL) and stirred
  7. customto form suspension
  8. concentrationThe reaction mixture was concentrated after 2 hours
  9. stirringof stirring at room temperature
  10. customthe crude residue was purified by reverse-phase chromatography (5-75-95% acetonitrile/water with 0.1% formic acid)

Sources & evidence

ORD record
ord-b31ac065605e4d88bd075e6b0237e6cb
Source dataset
uspto-grants-2009_06
Patent number
US07544695B2

Reaction notes

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