Carbonate Ion → N-(4-{[(4-Aminobiphenyl-3-yl)amino]carbonyl}phenyl)-2,8-diazaspiro[4.5]decane-2-carboxamide

HRID 2360566Notes

Reaction equation

HRID 2360566 reaction equation
[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]1[C:17]2([CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]2)[CH2:16][CH2:15][NH:14]1.[NH2:30][C:31]1[CH:32]=[C:33]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:34]=[CH:35][C:36]=1[NH:37]C(=O)OC(C)(C)C.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-]>ClCCl>[NH2:37][C:36]1[CH:35]=[CH:34][C:33]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[CH:32][C:31]=1[NH:30][C:8]([C:7]1[CH:11]=[CH:12][C:4]([NH:1][C:2]([N:14]2[CH2:15][CH2:16][C:17]3([CH2:18][CH2:19][NH:20][CH2:21][CH2:22]3)[CH2:13]2)=[O:3])=[CH:5][CH:6]=1)=[O:9]

Participants

7

Reactant 5

HCID 19660Carbonate IonHCID 81531DiisopropylethylamineHCID 27333234-Isocyanatobenzoyl chlorideHCID 23282900tert-Butyl 2,8-diazaspiro(4.5)decane-8-carboxylateHCID 57717454N-(3-Amino[1,1'-biphenyl]-4-yl)-carbamic Acid tert-Butyl Ester

Product 1

HCID 49805700N-(4-{[(4-Aminobiphenyl-3-yl)amino]carbonyl}phenyl)-2,8-diazaspiro[4.5]decane-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of stirring 4-isocyanatobenzoyl chloride (50 mg, 0.275 mmol) in 3 mL dichloromethane was added tert-butyl 2,8-diazaspiro[4.5]decane-8-carboxylate (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]+ 470.2, obs'd 470.1

Workup

  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)

Sources & evidence

ORD record
ord-357f8a2960dc45bca00909e80f73bdaf
Source dataset
uspto-grants-2014_04
Patent number
US08686020B2

Reaction notes

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