Triethylamine → HCID 44242494, compound

HRID 84461Notes

Reaction equation

HRID 84461 reaction equation
Cl.NC1C=CC2C3SC(C(N(C4C=CC=CC=4Cl)C)=O)=CC=3CCOC=2C=1.C(N(CC)CC)C.C(OCC(Cl)=O)C1C=CC=CC=1.C([O:54][CH2:55][C:56]([NH:58][C:59]1[CH:60]=[CH:61][C:62]2[C:68]3[S:69][C:70]([C:72]([N:74]([C:76]4[CH:81]=[CH:80][CH:79]=[CH:78][C:77]=4[Cl:82])[CH3:75])=[O:73])=[CH:71][C:67]=3[CH2:66][CH2:65][O:64][C:63]=2[CH:83]=1)=[O:57])C1C=CC=CC=1>C(Cl)Cl.C(O)(C(F)(F)F)=O.C(S(O)(=O)=O)(F)(F)F>[Cl:82][C:77]1[CH:78]=[CH:79][CH:80]=[CH:81][C:76]=1[N:74]([CH3:75])[C:72]([C:70]1[S:69][C:68]2[C:62]3[CH:61]=[CH:60][C:59]([NH:58][C:56](=[O:57])[CH2:55][OH:54])=[CH:83][C:63]=3[O:64][CH2:65][CH2:66][C:67]=2[CH:71]=1)=[O:73]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 177085Benzyloxyacetyl chlorideHCID 66868531HCID 66868531, compoundHCID 66868728HCID 66868728, compound

Product 1

HCID 44242494HCID 44242494, compoundYield 64%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 62406Trifluoromethanesulfonic acidSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 8-amino-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide HCl salt (1.0 g, 2.37 mmol) in 30 mL of DCM (dichloromethane, methylene chloride) was added triethylamine (1 mL, 7.12 mmol). The mixture was stirred at 0° C. for 10 min and BnOCH2COCl (0.53 g, 2.85 mmol) was added dropwise. After the addition was completed, the reaction mixture was raised to room temperature and stirred for another 2 hours. The mixture was quenched by water and extracted with EtOAc. The organic phases were combined, dried over Na2SO4 and evaporated to about 0.9 g of the crude product, which was used for the next step without further purification. A mixture of 8-(2-(benzyloxy)acetamido)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (0.6 g, 1.13 mmol) in TFA (5 mL) and CF3SO3H (2 mL) was stirred at 60° C. overnight. After removal of the solvent, the crude product was purified by prep. TLC to give about 320 mg of 158 (isolated yield: 64%). 1H NMR (DMSO-d6, 400 MHz): δ 9.77 (s, 1H), 7.63-7.35 (m, 7H), 6.47 (s, 1H), 5.64 (s, 1H), 4.11 (s, 2H), 3.94 (d, J=5.2 Hz, 2H), 3.23 (s, 3H), 2.88 (d, J=5.2 Hz, 2H). MS: (ESI+) 443.0

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was raised to room temperature
  3. stirringstirred for another 2 hours
  4. customThe mixture was quenched by water
  5. extractionextracted with EtOAc
  6. dry with materialdried over Na2SO4
  7. customevaporated to about 0.9 g of the crude product, which
  8. customwas used for the next step without further purification
  9. stirringwas stirred at 60° C. overnight
  10. customAfter removal of the solvent
  11. customthe crude product was purified by prep

Sources & evidence

ORD record
ord-12fcf343ed8142529e5f8c507237d724
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Reaction notes

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