Hydrochloric Acid → HCID 86662215, compound

HRID 2199535Notes

Reaction equation

HRID 2199535 reaction equation
C1COCC1.[CH3:6][O:7][C:8]1[C:13]2[CH2:14][CH2:15][C@@H:16]3[C@H:21]([C:12]=2[CH:11]=[CH:10][C:9]=1[O:23][CH3:24])[CH2:20][NH:19][C:18](=O)[CH2:17]3.[ClH:25]>CCOCC.CCO>[ClH:25].[CH3:6][O:7][C:8]1[C:13]2[CH2:14][CH2:15][C@@H:16]3[C@H:21]([C:12]=2[CH:11]=[CH:10][C:9]=1[O:23][CH3:24])[CH2:20][NH:19][CH2:18][CH2:17]3

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 86662217HCID 86662217, compound

Product 1

HCID 86662215HCID 86662215, compoundYield 59.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A flame-dried 1-neck flask was charged with 50 mL of distilled THF and 0.130 g (0.498 mmol) of the cis lactam 15a were added. A 1.0 M solution of BH3 in THF (2.49 mL, 2.49 mmol) was added dropwise to the flask and the reaction was heated at reflux overnight. The reaction was then cooled to room temperature, quenched carefully with H2O, and evaporated to about one-third the volume. Following the addition of 10 mL 2N HCl, the solution was stirred at ambient temperature for 4 h. The aqueous solution was washed once with Et2O, basified with NH4OH, and extracted with CH2Cl2 (3×25 mL). The organic layers were combined, dried over Na2SO4, filtered, and evaporated to yield a colorless residue, which was dissolved in Et2O and acidified with 6N HCl in EtOH. The solid that formed was collected by filtration to yield 0.084 g (0.297 mmol, 59.6%) of the isoquinoline HCl 17a as a white powder; mp 186° C. (dec). 1H NMR: (500 MHz, DMSO): δ 8.80 (bs, 2H, NH2); 6.87 (m, 2H, ArH); 3.75 (s, 3H, ArOCH3); 3.66 (s, 3H, ArOCH3); 3.18-3.15 (dd, 1H, J=4.2, 12.4 Hz, ArCHCH2NH2); 3.12-3.05 (m, 2H, CH2NH2CH2); 2.99-2.82 (m, 3H, ArCHCH2NH2CH2, ArCH2); 2.59-2.48 (m, 1H, ArCH2); 2.10-1.89 (m, 3H, ArCH2CH2CHCH2); 1.76-1.68 (bd, 1H, J=11.8 Hz, NH2CH2CH2); 1.62-1.54 (m, 1H, ArCH2CH2). ESIMS (M+H)=248.

Workup

  1. additionwere added
  2. temperaturethe reaction was heated
  3. temperatureat reflux overnight
  4. customquenched carefully with H2O
  5. customevaporated to about one-third the volume
  6. additionthe addition of 10 mL 2N HCl
  7. washThe aqueous solution was washed once with Et2O
  8. extractionextracted with CH2Cl2 (3×25 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated
  12. customto yield a colorless residue, which
  13. customThe solid that formed
  14. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-8c122e5e00c742aba4204c05fdb470c0
Source dataset
uspto-grants-2016_06
Patent number
US09359303B2

Reaction notes

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