1,2-Dichloroethane → HCID 68777518, compound

HRID 1253872Notes

Reaction equation

HRID 1253872 reaction equation
[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.[NH:54]1[C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][C:59]=2[CH2:58][NH:57][CH2:56][C:55]1=[O:65]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[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](=[O:13])[N:57]1[CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=2[NH:54][C:55](=[O:65])[CH2:56]1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acidHCID 68639611HCID 68639611, compound

Product 1

HCID 68777518HCID 68777518, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (90 mg, 0.26 mmol) in dry DCM (10 mL), was added HOBT (47 mg, 0.34 mmol), EDC (67 mg, 0.34 mmol) and DIPEA (0.24 mL, 1.35 mmol). The reaction mixture was stirred at r.t. for 10 min. A solution of 1,3,4,5-Tetrahydro-benzo[e][1,4]diazepin-2-one trifluoroacetate (74 mg, 0.26 mmol) in dry DCM (5 mL) was added and the reaction mixture 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 sequentially with 10% HCl solution (10 mL) and saturated sodium bicarbonate solution (10 mL). 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, 2:3 EtOAc:Pet.Ether) to afford [(R)-3-Oxo-3-(2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl ester (80 mg, 62%) as a white solid.

Workup

  1. stirringthe reaction mixture was stirred at r.t. overnight under nitrogen atmosphere
  2. customAfter the completion of the reaction
  3. extractionthe crude product was extracted with DCM (10 mL)
  4. washwashed sequentially with 10% HCl solution (10 mL) and saturated sodium bicarbonate solution (10 mL)
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto afford the crude compound, which
  10. customwas purified by column chromatography (silica gel, 2:3 EtOAc:Pet.Ether)

Sources & evidence

ORD record
ord-af3668c634a244609858e56a99ddcccb
Source dataset
uspto-grants-2013_06
Patent number
US08455479B2

Reaction notes

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