Water → 9-tert-butyl-2-bromo-3-methoxy-13-(2-thienyl)-5,6,9,10,11,12-hexahydro-8H-azepino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8-one

HRID 1971649Notes

Reaction equation

HRID 1971649 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:15](=O)[C:16]([N:18]([C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:19][CH2:20][CH2:21][C:22]#[C:23][C:24]3[S:25][CH:26]=[CH:27][CH:28]=3)=[O:17])[CH:9]2C(O)=O)=[CH:4][C:3]=1[O:34][CH3:35].C([O-])(=O)C.[Na+].O.[NH4+].[OH-]>C(OC(=O)C)(=O)C>[C:29]([N:18]1[CH2:19][CH2:20][CH2:21][C:22]2[C:23]([C:24]3[S:25][CH:26]=[CH:27][CH:28]=3)=[C:9]3[C:10]4[CH:11]=[C:2]([Br:1])[C:3]([O:34][CH3:35])=[CH:4][C:5]=4[CH2:6][CH2:7][N:8]3[C:15]=2[C:16]1=[O:17])([CH3:30])([CH3:32])[CH3:31]

Participants

6

Reactant 4

HCID 962WaterHCID 14923Ammonium HydroxideHCID 517045Sodium AcetateHCID 581249487-Bromo-2-(2-(tert-butyl(5-(thiophen-2-yl)pent-4-ynyl)amino)-2-oxoacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid

Product 1

HCID 581248529-tert-butyl-2-bromo-3-methoxy-13-(2-thienyl)-5,6,9,10,11,12-hexahydro-8H-azepino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8-oneYield 85.3%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2.9 g of 3c in 30 ml of acetic anhydride and 3 g of sodium acetate was heated with stirring at 100° C. for ½ hr. The mixture was cooled to RT. Then, 100 ml of water was added and stirring was prolonged for 1 hr. The reaction mixture was neutralized by dropwise addition of cold conc. aq. NH4OH solution, the product was extracted with ethyl acetate and the organic layer was washed, dried and concentrated. The residue was treated with diisopropyl ether, to provide 2.2 g of 3d as white crystalline material; Mp 232-233° C.; MS-ESI: [M+1] 499.15 and 501.19. Rf (heptane/ethyl acetate 1/1) 0.50

Workup

  1. temperatureThe mixture was cooled to RT
  2. stirringstirring
  3. waitwas prolonged for 1 hr
  4. extractionthe product was extracted with ethyl acetate
  5. washthe organic layer was washed
  6. customdried
  7. concentrationconcentrated
  8. additionThe residue was treated with diisopropyl ether

Sources & evidence

ORD record
ord-3cc0f1cee6b7424cb14903caf48e3fbc
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

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