1,2-Dichloroethane → HCID 69655738, compound

HRID 857751Notes

Reaction equation

HRID 857751 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:17]2[CH:21]=[N:20][CH:19]=[N:18]2)=[C:6]([CH:16]=1)[CH2:7][NH:8][C:9](=[O:15])[C@@H:10]1[CH2:14][CH2:13][CH2:12][NH:11]1.[C:22]([O:26][C:27]([NH:29][C@@H:30]([C:35](O)=[O:36])[CH2:31][CH:32]1[CH2:34][CH2:33]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C1C=C2N=NN(O)C2=CC=1.O.C(Cl)CCl.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:22]([O:26][C:27]([NH:29][C@@H:30]([C:35]([N:11]1[CH2:12][CH2:13][CH2:14][C@H:10]1[C:9]([NH:8][CH2:7][C:6]1[CH:16]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[N:17]1[CH:21]=[N:20][CH:19]=[N:18]1)=[O:15])=[O:36])[CH2:31][CH:32]1[CH2:34][CH2:33]1)=[O:28])([CH3:24])([CH3:25])[CH3:23]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 2756015(R)-2-((tert-Butoxycarbonyl)amino)-3-cyclopropylpropanoic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 69656007HCID 69656007, compound

Product 1

HCID 69655738HCID 69655738, compoundYield 92.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-[5-chloro-2-(1H1,2,4-triazol-1-yl)benzyl]-L-prolinamide (Example 27, Step B, 0.046 g, 0.121 mmol), N-(tert-butoxycarbonyl)-3-cyclopropyl-D-alanine (30 mg, 0.121 mmol), and HOBt hydrate (20 mg, 0.145 mmol) in DMF (3 mL) was added EDC (0.028 g, 0.145 mmol). Diisopropylethylamine (0.083 mL, 0.484 mmol) was added and the mixture was stirred at ambient temperature for 18 hours, at which time HPLC analysis indicated complete consumption of the proline starting material. The DMF was removed under reduced pressure and the residue was partitioned between EtOAc (50 mL) and 10% aqueous Na2CO3. The EtOAc layer was separated, washed with water and brine, dried over anhydrous MgSO4, and filtered. The filtrate solvent was removed under reduced pressure to give N-(tert-butoxycarbonyl)-3-cyclopropyl-D-alanyl-N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide as a gum (0.058 g). HPLC RT=2.18 min, Method B; LCMS (M+H): 517, 519.

Workup

  1. customconsumption of the proline starting material
  2. customThe DMF was removed under reduced pressure
  3. customthe residue was partitioned between EtOAc (50 mL) and 10% aqueous Na2CO3
  4. customThe EtOAc layer was separated
  5. washwashed with water and brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe filtrate solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-9598a65206b94efeb5f602ba2082e1d9
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

Loading…