Trifluoroacetic acid → HCID 22396609, compound

HRID 1356336Notes

Reaction equation

HRID 1356336 reaction equation
[Br:1][C:2]1[C:3]2[C:4]3[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21][C:5]=3[N:6]([CH2:11][C:12]([NH:14][C:15]3[S:16][CH:17]=[C:18]([CH3:20])[N:19]=3)=[O:13])[C:7]=2[CH:8]=[CH:9][CH:10]=1.C(C(O)=O)(F)(F)F>C(Cl)Cl>[Br:1][C:2]1[C:3]2[C:4]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21][C:5]=3[N:6]([CH2:11][C:12]([NH:14][C:15]3[S:16][CH:17]=[C:18]([CH3:20])[N:19]=3)=[O:13])[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 22396748HCID 22396748, compound

Product 1

HCID 22396609HCID 22396609, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 10-bromo-6-{2-[(4-methyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.13 g, 0.24 mmol) was dissolved in CH2Cl2 (5 mL). CF3CO2H (0.5 mL, 0.74 g, 6.5 mmol) was added. The reaction mixture was stirred at rt under N2 for 46 h. The reaction mixture was partitioned between 1N NaOH (60 mL) and EtOAc (350 mL). The aqueous layer was back extracted with EtOAc (100 mL). The combined organic layers were washed with brine (25 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was flash chromatographed (10% CH3OH/CH2Cl2 containing 0.05% 7N NH3/CH3OH) and 2-(10-bromo-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-N-(4-methyl-1,3-thiazol-2-yl)acetamide was obtained in 28% yield. 1H NMR (400 MHz, CD3OD) δ 2.33, 3.02-3.09, 3.14-3.21, 3.55-3.63, 5.16, 6.67, 6.97, 7.21, 7.30; MS (ESI+) for C18H19BrN4OS m/z 420.8 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between 1N NaOH (60 mL) and EtOAc (350 mL)
  2. extractionThe aqueous layer was back extracted with EtOAc (100 mL)
  3. washThe combined organic layers were washed with brine (25 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customchromatographed (10% CH3OH/CH2Cl2 containing 0.05% 7N NH3/CH3OH)

Sources & evidence

ORD record
ord-af2e85cbd4314d75bd840d8f757a1862
Source dataset
uspto-grants-2003_07
Patent number
US06586421B2

Reaction notes

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