1,2-Dichloroethane → [3-(1-methyl-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-3-oxo-(R)-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl ester

HRID 1253880Notes

Reaction equation

HRID 1253880 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.[CH3:47][N:48]1[C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=2[CH2:52][NH:51][CH2:50][C:49]1=[O:59]>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]([N:51]1[CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2[N:48]([CH3:47])[C:49](=[O:59])[CH2:50]1)=[O:13])([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 187582601-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-one

Product 1

HCID 68638321[3-(1-methyl-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-3-oxo-(R)-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl esterYield 80.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (80 mg, 0.24 mmol) in dry DCM (10 mL), was added HOBT (42 mg, 0.31 mmol), EDC (59 mg, 0.31 mmol) and DIPEA (0.20 mL, 1.2 mmol). The reaction mixture was stirred at r.t. for 10 min. A solution of 1-methyl-1,3,4,5-tetrahydrobenzo (e) [1,4]diazepin-2-one trifluoroacete (70 mg, 0.24 mmol) in dry DCM (5 mL) was added and the reaction mixture was stirred at r.t. overnight. 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 solution of sodium bicarbonate (10 mL). The organic layer was separated and washed with brine and dried over Na2SO4. The solvents were removed in vacuo to afford the crude compound, which was purified by column chromatography (silica gel, 3:7 EtOAc:Pet.Ether) to afford 2 [3-(1-methyl-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-3-oxo-(R)-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl ester (95 mg, 78%) as viscous oil.

Workup

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

Sources & evidence

ORD record
ord-31efe1a910d5417ca4d9304f34432798
Source dataset
uspto-grants-2013_06
Patent number
US08455479B2

Reaction notes

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