1-Hydroxybenzotriazole → (4-[2-((S)-2-((S)-2-acetylamino-3-phenyl-propionylamino)-3-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-propionylamino)-ethyl]-phenyl]-acetic acid t-butyl ester

HRID 1592053Notes

Reaction equation

HRID 1592053 reaction equation
[C:1]([NH:4][C@@H:5]([CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:24][C:23](=[O:25])[N:22]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[S:21]2(=[O:36])=[O:35])=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])(=[O:3])[CH3:2].[C:44]([O:48][C:49](=[O:60])[CH2:50][C:51]1[CH:56]=[CH:55][C:54]([CH2:57][CH2:58][NH2:59])=[CH:53][CH:52]=1)([CH3:47])([CH3:46])[CH3:45].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.C(Cl)Cl.CN(C=O)C.C(Cl)Cl.CCOC(C)=O>[C:44]([O:48][C:49](=[O:60])[CH2:50][C:51]1[CH:52]=[CH:53][C:54]([CH2:57][CH2:58][NH:59][C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[C@@H:5]([NH:4][C:1](=[O:3])[CH3:2])[CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C:23](=[O:25])[N:22]([CH2:26][C:27]4[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=4)[S:21]3(=[O:36])=[O:35])=[CH:16][CH:15]=2)=[CH:55][CH:56]=1)([CH3:45])([CH3:47])[CH3:46]

Participants

9

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14775459tert-Butyl 2-(4-(2-aminoethyl)phenyl)acetateHCID 67139907(S)-2-((S)-2-acetylamino-3-phenyl-propionylamino)-3-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-propionic acid

Product 1

HCID 67140038(4-[2-((S)-2-((S)-2-acetylamino-3-phenyl-propionylamino)-3-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-propionylamino)-ethyl]-phenyl]-acetic acid t-butyl ester

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

The title C compound, (S)-2-((S)-2-acetylamino-3-phenyl-propionylamino)-3-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-propionic acid (83.4 mg, 0.137 mmol) is dissolved in DMF (2 mL) and a solution of [4-(2-amino-ethyl)phenyl]-acetic acid t-butyl ester (32.2 mg, 0.137 mmol) in CH2Cl2 (0.5 mL) is added followed by a solution of HOBt (21.9 mg, 0.143 mmol) in DMF:CH2Cl2 (50:50, 0.5 mL), and finally EDCl (27.6 mg, 0.143 mmol) and TEA (0.020 mL, 0.143 mmol) as a slurry in CH2Cl2 (0.5 mL). The reaction is mixed well to give a homogeneous solution. After 3 h, EtOAc (100 mL) is added and the reaction is washed three times with 2N aqueous HCl (50 mL) and saturated aqueous NaHCO3 (50 mL). EtOAc layer is dried over anhydrous Na2SO4 and concentrated to yield {4-[2-((S)-2-((S)-2-acetylamino-3-phenyl-propionylamino)-3-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-propionylamino)-ethyl]-phenyl}-acetic acid t-butyl ester as an oil.

Workup

  1. additionThe reaction is mixed well
  2. customto give a homogeneous solution
  3. washthe reaction is washed three times with 2N aqueous HCl (50 mL) and saturated aqueous NaHCO3 (50 mL)
  4. dry with materialEtOAc layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-034bc266fe2e4adda8608681cd8cb3ba
Source dataset
uspto-grants-2007_11
Patent number
US07291635B2

Reaction notes

Loading…