1,2-Dichloroethane → HCID 68777526, compound

HRID 1253909Notes

Reaction equation

HRID 1253909 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[F:39])[CH2:10][C:11]([N:13]1[CH2:22][C:21]2[N:17]([CH:18]=[N:19][C:20]=2[C:23]([OH:25])=O)[C:16]2[CH:26]=[CH:27][CH:28]=[CH:29][C:15]=2[CH2:14]1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:40]1[CH:41]=CC2N(O)N=[N:46][C:44]=2[CH:45]=1.C(Cl)CCl.CCN(C(C)C)C(C)C.N1CCCC1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[F:39])[CH2:10][C:11](=[O:12])[N:13]1[CH2:22][C:21]2[N:17]([CH:18]=[N:19][C:20]=2[C:23]([N:46]2[CH2:41][CH2:40][CH2:45][CH2:44]2)=[O:25])[C:16]2[CH:26]=[CH:27][CH:28]=[CH:29][C:15]=2[CH2:14]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 68777038HCID 68777038, compound

Product 1

HCID 68777526HCID 68777526, compoundYield 83.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-5-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid (60 mg, 0.11 mmol) in dry DCM (15 mL), was added HOBT (19 mg, 0.14 mmol), EDC (27 mg, 0.14 mmol) and DIPEA (0.08 mL; 0.46 mmol) and the reaction mixture was stirred for 10 min. Pyrrolidine (0.02 mL, 0.24 mmol) was added and the reaction 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 (15 mL) and washed 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, 3:7 to 9:1 EtOAc:Pet.Ether) to afford (R)-[3-oxo-3-[3-(pyrrolidine-1-carbonyl)-4H,6H-2,5,10b-triaza-benzo[e]azulen-5-yl]-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl ester (55 mg, 83%) as a solid.

Workup

  1. stirringthe reaction was stirred at r.t. overnight under nitrogen atmosphere
  2. customAfter the completion of the reaction
  3. extractionthe crude product was extracted with DCM (15 mL)
  4. washwashed 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, 3:7 to 9:1 EtOAc:Pet.Ether)

Sources & evidence

ORD record
ord-45a766f0f47c4065bebff363a3316147
Source dataset
uspto-grants-2013_06
Patent number
US08455479B2

Reaction notes

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