1,2-Dichloroethane → N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[(1-tert-butoxycarbonyl-2-methylazetidin-2-yl)carbonyl]-L-prolinamide

HRID 857771Notes

Reaction equation

HRID 857771 reaction equation
C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([N:39]2[CH:43]=[N:42][N:41]=[N:40]2)=[C:28]([CH:38]=1)[CH2:29][NH:30][C:31](=[O:37])[C@@H:32]1[CH2:36][CH2:35][CH2:34][NH:33]1.[C:44]([O:48][C:49]([N:51]1[CH2:54][CH2:53][C:52]1([CH3:58])[C:55](O)=[O:56])=[O:50])([CH3:47])([CH3:46])[CH3:45]>CN(C=O)C>[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([N:39]2[CH:43]=[N:42][N:41]=[N:40]2)=[C:28]([CH:38]=1)[CH2:29][NH:30][C:31](=[O:37])[C@@H:32]1[CH2:36][CH2:35][CH2:34][N:33]1[C:55]([C:52]1([CH3:58])[CH2:53][CH2:54][N:51]1[C:49]([O:48][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:50])=[O:56]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 218663321-[(Tert-butoxy)carbonyl]-2-methylazetidine-2-carboxylic acidHCID 69656419N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide hydrochloride

Product 1

HCID 69656015N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[(1-tert-butoxycarbonyl-2-methylazetidin-2-yl)carbonyl]-L-prolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (0.104 g, 0.54 mmol), HOAt (24.6 mg, 0.18 mmol), NMM (0.079 mL, 0.72 mmol), and N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide hydrochloride (Example 26, Step B, 0.143 g, 0.42 mmol) were added to a stirred solution of racemic 1-(tert-butoxycarbonyl)-2-methylazetidine-2-carboxylic acid (0.143 g, 0.36 mmol in DMF (1.1 mL). After 3 h at room temperature the reaction was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo. The two diastereomers were separated and purified by reverse phase HPLC. The more polar diastereomer was concentrated in vacuo. N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[(1-tert-butoxycarbonyl-2-methylazetidin-2-yl)carbonyl]-L-prolinamide (diastereomer A) was obtained as a glass. MS m/z=404.6).

Workup

  1. customAfter 3 h at room temperature the reaction was partitioned between EtOAc and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe two diastereomers were separated
  6. custompurified by reverse phase HPLC
  7. concentrationThe more polar diastereomer was concentrated in vacuo

Sources & evidence

ORD record
ord-8781b70d0e0f4e7eb12b04d282b9cb0c
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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