Ethylamine → HCID 57389113, compound

HRID 2401361Notes

Reaction equation

HRID 2401361 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[C:19]([CH3:22])=[N:20][O:21][C:11]=3[C@H:10]([CH2:23][C:24]([O:26]C(C)(C)C)=O)[N:9]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.[CH2:38]([NH2:40])[CH3:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O.CO.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[C:19]([CH3:22])=[N:20][O:21][C:11]=3[C@H:10]([CH2:23][C:24]([NH:40][CH2:38][CH3:39])=[O:26])[N:9]=2)=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 6341EthylamineHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57344511HCID 57344511, compound

Product 1

HCID 57389113HCID 57389113, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a round bottomed flask was added tert-butyl 2-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetate (0.019 g, 0.046 mmol), CH2Cl2 (2 mL), and TFA (0.400 mL, 5.19 mmol). The reaction was stirred for 1 h before being concentrated. The crude residue was dissolved in DMF (1 mL) and ethylamine (0.032 mL, 0.064 mmol), HATU (0.026 g, 0.068 mmol), and Hunig's base (0.024 mL, 0.137 mmol) were added. The reaction was stirred at room temperature for 1 h before diluting with water and methanol and purification via preparatory HPLC. The fractions were neutralized and the aqueous extracted with CH2Cl2. The combined organics were dried over Na2SO4, filtered, and concentrated. The crude residue was purified via Biotage (EtOAc/hex) to afford 2-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)-N-ethylacetamide (0.0068 g, 0.017 mmol). 1H NMR (400 MHz, DMSO-d6) δ 8.27-8.13 (m, 1H), 7.83 (d, J=7.3 Hz, 1H), 7.72 (d, J=1.6 Hz, 1H), 7.49-7.36 (m, 4H), 7.34-7.25 (m, 2H), 4.42-4.23 (m, 1H), 3.14 (dd, J=6.98, 12.7 Hz, 4H), 2.51 (s, 3H), 1.07 (t, J=7.2 Hz, 3H); LC/MS m/z 394 [M+H]+.

Workup

  1. concentrationbefore being concentrated
  2. dissolutionThe crude residue was dissolved in DMF (1 mL)
  3. stirringThe reaction was stirred at room temperature for 1 h
  4. extractionthe aqueous extracted with CH2Cl2
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified via Biotage (EtOAc/hex)

Sources & evidence

ORD record
ord-85f847c59db64fba9a22073a9008c444
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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