Triethylamine → HCID 16049336, compound

HRID 1873500Notes

Reaction equation

HRID 1873500 reaction equation
[CH2:1]([N:3](CC)CC)[CH3:2].C1C[N:11]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(OC([C:48]1[CH2:49][C:50]([C:66]([OH:68])=O)=[CH:51][C:52]2[CH:58]=[CH:57][C:56]([C:59]([F:65])([F:64])[C:60]([F:63])([F:62])[F:61])=[CH:55][C:53]=2[N:54]=1)=O)(C)(C)C.Cl.C(N)C>CN(C=O)C>[NH2:11][C:48]1[CH2:49][C:50]([C:66]([NH:3][CH2:1][CH3:2])=[O:68])=[CH:51][C:52]2[CH:58]=[CH:57][C:56]([C:59]([F:64])([F:65])[C:60]([F:61])([F:62])[F:63])=[CH:55][C:53]=2[N:54]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11198Ethylamine hydrochlorideHCID 2724699PyBOPHCID 86623313HCID 86623313, compound

Product 1

HCID 16049336HCID 16049336, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of triethylamine (76 mg, 0.750 mmol), PyBOP (143 mg, 0.275 mmol) and (1E,4E)-2-(tert-butoxycarbonyl)-8-(perfluoroethyl)-3H-benzo[b]azepine-4-carboxylic acid (105 mg, 0.250 mmol) in DMF (4 mL) was added ethylamine hydrochloride (41 mg, 0.500 mmol). After stirring for 14 hours the mixture was partitioned between EtOAc (50 mL) and brine (100 mL). The phases were separated and the organic layer was washed with water (3×100 mL). The combined organics were dried and concentrated. The crude residue was taken up in CH2Cl2/TFA (˜1:1, 50 mL) and stirred at room temperature for 2 hours. The volatiles were removed under vacuum and the residue was partitioned between EtOAc and 10% Na2CO3 (1:1, 100 mL). The phases were separated and the aqueous was extracted with EtOAc (2×50 mL). The combined organics were dried and concentrated. The concentrate was purified via preparative TLC (2, 0.5 mm plates eluting with 10% MeOH/CH2Cl2 with 4-6 drops of NH4OH) to provide (1E,4E)-2-amino-N-ethyl-8-(perfluoroethyl)-3H-benzo[b]azepine-4-carboxamide (6.5 mg, 8%). 1H NMR (CDCl3) δ 1.26 (t, 2H), 2.94 (s, 2H), 3.41-3.48 (m, 2H), 5.15 (br s, 1H), 6.08 (br s, 1H), 7.16 (s, 1H), 7.22 (d, 1H), 7.42 (d, 1H), 7.47 (s, 1H).

Workup

  1. customwas partitioned between EtOAc (50 mL) and brine (100 mL)
  2. customThe phases were separated
  3. washthe organic layer was washed with water (3×100 mL)
  4. customThe combined organics were dried
  5. concentrationconcentrated
  6. stirringstirred at room temperature for 2 hours
  7. customThe volatiles were removed under vacuum
  8. customthe residue was partitioned between EtOAc and 10% Na2CO3 (1:1, 100 mL)
  9. customThe phases were separated
  10. extractionthe aqueous was extracted with EtOAc (2×50 mL)
  11. customThe combined organics were dried
  12. concentrationconcentrated
  13. customThe concentrate was purified via preparative TLC (2, 0.5 mm plates eluting with 10% MeOH/CH2Cl2 with 4-6 drops of NH4OH)

Sources & evidence

ORD record
ord-dcbe9ca1e3d04740b5188dfa8f6f2a6d
Source dataset
uspto-grants-2012_11
Patent number
US08304407B2

Reaction notes

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