1,2-Dichloroethane → (R)-5-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-5,6-dihydro-4H-2,5,10b triaza-benzo[e]azulene-3-carboxylic acid ethyl ester

HRID 1253905Notes

Reaction equation

HRID 1253905 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.[CH2:54]([O:56][C:57]([C:59]1[N:60]=[CH:61][N:62]2[C:68]=1[CH2:67][NH:66][CH2:65][C:64]1[CH:69]=[CH:70][CH:71]=[CH:72][C:63]2=1)=[O:58])[CH3:55]>C(Cl)Cl>[CH2:54]([O:56][C:57]([C:59]1[N:60]=[CH:61][N:62]2[C:68]=1[CH2:67][N:66]([C:11](=[O:13])[CH2:10][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:65][C:64]1[CH:69]=[CH:70][CH:71]=[CH:72][C:63]2=1)=[O:58])[CH3:55]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acidHCID 687776935,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester trifluoroacetate

Product 1

HCID 68776113(R)-5-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-5,6-dihydro-4H-2,5,10b triaza-benzo[e]azulene-3-carboxylic acid ethyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluoro-phenyl)butanoic acid (80 mg, 0.26 mmol) in dry DCM (15 mL), was added HOBT (42 mg, 0.31 mmol); EDC (60 mg, 0.31 mmol) and DIPEA (0.21 mL, 1.21 mmol) and the reaction mixture was stirred for 10 min. 5,6-Dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester trifluoroacetate (98 mg, 0.26 mmol) in DCM (5 mL) was added and the reaction was stirred at r.t. overnight under nitrogen atmosphere. After the completion of the reaction, as confirmed by TLC, the crude product was extracted with DCM (10 mL) and washed with 10% HCl solution (10 mL) and saturated sodium bicarbonate solution (10 mL) sequentially. The organic layer was separated, washed with water, dried over Na2SO4 and concentrated in vacuo to afford the crude compound, which was purified by column chromatography (silica gel, 3:7 EtOAc:Pet.Ether) to afford (R)-5-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester (105 mg, 77%) as a viscous oil.

Workup

  1. customAfter the completion of the reaction
  2. extractionthe crude product was extracted with DCM (10 mL)
  3. washwashed with 10% HCl solution (10 mL) and saturated sodium bicarbonate solution (10 mL) sequentially
  4. customThe organic layer was separated
  5. washwashed with water
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto afford the crude compound, which
  9. customwas purified by column chromatography (silica gel, 3:7 EtOAc:Pet.Ether)

Sources & evidence

ORD record
ord-e17530f55601464284321269a828e8c0
Source dataset
uspto-grants-2013_06
Patent number
US08455479B2

Reaction notes

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