Hydrochloric Acid → HCID 131724551, compound

HRID 1836597Notes

Reaction equation

HRID 1836597 reaction equation
[CH:1]1[CH:10]=[CH:9][C:8]2[O:11][CH2:12][CH2:13][CH2:14][N:6]3[C:7]=2[C:2]=1[C@H:3]1[CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][C@H:4]1[CH2:5]3.FC(F)(F)C(O)=O.[ClH:32].CCOCC>C(Cl)Cl.CCOCC.C(O)C>[ClH:32].[ClH:32].[CH:1]1[CH:10]=[CH:9][C:8]2[O:11][CH2:12][CH2:13][CH2:14][N:6]3[C:7]=2[C:2]=1[C@H:3]1[CH2:17][NH:16][CH2:15][C@H:4]1[CH2:5]3

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 131724552HCID 131724552, compound

Product 1

HCID 131724551HCID 131724551, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21585056Diethyl ether ethanolSolvent

Procedure

To absolution of (+)-cis tert-butyl 6,7,9a,10,12,12a-hexahydro-5H-[1,4]oxazepino[2,3,4-ij]pyrrolo[3,4-c]quinoline-11(9H)-carboxylate (250 mg, 0.76 mmol) in 15 mL of methylene chloride was added trifluoroacetic acid (4 mL). This mixture was stirred at ambient temperature for 2 h and then concentrated in vacuo. The residue was basified with sat'd aq Na2CO3 and extracted with chloroform. The organics were washed with brine, dried (K2CO3) and concentrated in vacuo to afford the free base. This material was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and the product containing fractions were concentrated, basified with sat'd aq Na2CO3 and extracted twice with ethyl acetate. The organics were washed with brine, dried (Na2SO4) and concentrated to a free base. A portion of the residue (30 mg, 0.13 mmol) was taken up in about 4:1 ether/ethanol and then there was added 2M HCl in ether (0.2 mL, 0.39 mmol). The resulting solid was filtered, washed twice with ether and dried in vacuo to afford the title compound of EXAMPLE 121 as an off-white powder. 1H NMR (dmso-D6) δ: 9.52 (broad s, 1H), 9.30 (broad s, 1H), 6.90-6.83 (m, 1H), 6.75-6.70 (m, 2H), 4.60 (dt, 1H, J=12.0, 5.1 Hz), 3.77-3.63 (m, 2H), 3.52-3.45 (m, 1H), 3.40-3.25 (m, 2H), 3.19-3.06 (m, 2H), 3.05-2.85 (m, 2H), 2.84 (t, 1H, J=12.0 Hz), 2.65-2.55 (m, 1H), 2.08-1.97 (m, 1H), 1.90-1.79 (m, 1H). LRMS (ES)+: 231.0 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. extractionextracted with chloroform
  3. washThe organics were washed with brine
  4. dry with materialdried (K2CO3)
  5. concentrationconcentrated in vacuo
  6. customto afford the free base
  7. customThis material was purified by preparative HPLC (
  8. washC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and the product
  9. additioncontaining fractions
  10. concentrationwere concentrated
  11. extractionextracted twice with ethyl acetate
  12. washThe organics were washed with brine
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated to a free base
  15. filtrationThe resulting solid was filtered
  16. washwashed twice with ether
  17. customdried in vacuo

Sources & evidence

ORD record
ord-71b4280ea8c84ecea3b9f199347ee5d0
Source dataset
uspto-grants-2004_08
Patent number
US06777406B2

Reaction notes

Loading…