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 1253905ノート

反応式

HRID 1253905 の反応式
[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]

参加物

7

反応物 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

生成物 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 ester収率 77%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-e17530f55601464284321269a828e8c0
出典データセット
uspto-grants-2013_06
特許番号
US08455479B2

反応ノート

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