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 1253905노트

반응식

HRID 1253905 반응식
[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]

참가 물질

7

반응물 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

생성물 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 ester수율 77%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-e17530f55601464284321269a828e8c0
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455479B2

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