Propylamine → tert-butyl (1E,4E)-4-(propylcarbamoyl)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepin-2-ylcarbamate

HRID 593427Notes

Reaction equation

HRID 593427 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH2:10][C:11]([C:33]([OH:35])=O)=[CH:12][C:13]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([N:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)=[O:27])=[CH:22][CH:21]=3)=[CH:16][C:14]=2[N:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=[CH:38][C:39]2N(O)N=[N:42][C:40]=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.C(N)CC>CN(C=O)C.CCOC(C)=O>[CH2:40]([NH:42][C:33]([C:11]1=[CH:12][C:13]2[CH:19]=[CH:18][C:17]([C:20]3[CH:21]=[CH:22][C:23]([C:26]([N:28]4[CH2:29][CH2:30][CH2:31][CH2:32]4)=[O:27])=[CH:24][CH:25]=3)=[CH:16][C:14]=2[N:15]=[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:10]1)=[O:35])[CH2:39][CH3:38]

Participants

8

Reactant 5

HCID 7852PropylamineHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 66960164(1E,4E)-2-(tert-butoxycarbonylamino)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxylic acid

Product 1

HCID 86652677tert-butyl (1E,4E)-4-(propylcarbamoyl)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepin-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (1E,4E)-2-(tert-butoxycarbonylamino)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxylic acid (200 mg, 0.42 mmol), HOBt (114 mg, 0.84 mmol), and EDCI (161 mg, 0.84 mmol) in DMF (5 mL) was stirred for 1 h at room temperature. To this mixture was added triethylamine (0.12 mL, 0.84 mmol) and propan-1-amine (0.043 mL, 0.53 mmol) at room temperature. The resulting solution was stirred for additional 2 h. The reaction mixture was diluted with EtOAc (5 mL) and washed with sat'd aq NH4Cl. The aqueous layer was seperated and extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine (5 mL), sat'd aq NaHCO3 (5 mL), and brine (5 mL). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude tert-butyl (1E,4E)-4-(propylcarbamoyl)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepin-2-ylcarbamate that was used directly without further purification.

Workup

  1. stirringThe resulting solution was stirred for additional 2 h
  2. washwashed with sat'd aq NH4Cl
  3. customThe aqueous layer was seperated
  4. extractionextracted with EtOAc (3×5 mL)
  5. washThe combined organic layers were washed with brine (5 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-10c0937670894129b2a68169cc691663
Source dataset
uspto-grants-2016_01
Patent number
US09242964B2

Reaction notes

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