Triphenylphosphine → (s)-2-Amino-n-(1-carbamoyl-4-guanidino-butyl)-5-[2-(2,4-dichlorophenyl)ethoxy]benzamide

HRID 433036

反応式

HRID 433036 の反応式
[NH2:1][C@H:2]([C:24]([OH:26])=O)[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:23])[N:8](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O.[OH:27][C:28]1[CH:29]=[CH:30][C:31]([N+:37]([O-])=O)=[C:32]([CH:36]=1)[C:33]([OH:35])=O.CC(C)[N:42]=C=NC(C)C.C1C=CC2N(O)N=NC=2C=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:78][C:79]1[CH:84]=[C:83]([Cl:85])[CH:82]=[CH:81][C:80]=1[CH2:86][CH2:87]O.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CN(C=O)C.C1COCC1>[NH2:37][C:31]1[CH:30]=[CH:29][C:28]([O:27][CH2:87][CH2:86][C:80]2[CH:81]=[CH:82][C:83]([Cl:85])=[CH:84][C:79]=2[Cl:78])=[CH:36][C:32]=1[C:33]([NH:1][C@H:2]([C:24](=[O:26])[NH2:42])[CH2:3][CH2:4][CH2:5][NH:6][C:7]([NH2:8])=[NH:23])=[O:35]

参加物

10

反応物 7

HCID 11776TriphenylphosphineHCID 118825-Hydroxy-2-nitrobenzoic acidHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 27340992,4-Dichlorophenethyl alcoholHCID 5363146Diisopropyl azodicarboxylateHCID 178454311HCID 178454311、化合物

生成物 1

HCID 178512851(s)-2-Amino-n-(1-carbamoyl-4-guanidino-butyl)-5-[2-(2,4-dichlorophenyl)ethoxy]benzamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Rink resin (306 mg; loading 0.43 mmol/g) functionalized with Arg(Boc)2 was coupled with 146 mg of 5-hydroxy-2-nitrobenzoic acid in the presence of DIC (136 mg) and HOBt (140 mg) in DMF (2 ml) for 3 h at room temperature. The resin was then washed and treated with a 15% solution of benzyltrimethylammonium hydroxide in DMF for 60 min. The resin was washed with DMF, 10% acetic acid in DMF, DMF and DCM and dried in vacuo for 4 h. The dried resin was washed with anhydrous THF and mixed with 534 mg (2 mmol) of triphenylphosphane, 422 mg (2 mmol) of 2-(2,4-dichlorophenyl)ethanol and 400 μl (2 mmol) of DIAD in dry THF. The mixture was kept overnight at room temperature. The resin was washed and treated with 415 mg of tin dichloride monohydrate in 2 ml of DMF and 0.5 ml of trifluoroethanol. The reduction was continued overnight at room temperature. The resin was washed and dried, and the final product was cleaved off and processed as described in Example 1.

後処理

  1. washThe resin was then washed
  2. additiontreated with a 15% solution of benzyltrimethylammonium hydroxide in DMF for 60 min
  3. washThe resin was washed with DMF, 10% acetic acid in DMF, DMF and DCM
  4. customdried in vacuo for 4 h
  5. washThe dried resin was washed with anhydrous THF
  6. washThe resin was washed
  7. additiontreated with 415 mg of tin dichloride monohydrate in 2 ml of DMF and 0.5 ml of trifluoroethanol
  8. waitThe reduction was continued overnight at room temperature
  9. washThe resin was washed
  10. customdried

出典と根拠

ORDレコード
ord-5f2d0b808a76495195fdc7ec8cb0a7f9
出典データセット
uspto-grants-2003_12
特許番号
US06664393B2

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