Hydrochloric Acid → HCID 131723851, compound

HRID 1266017Notes

Reaction equation

HRID 1266017 reaction equation
[O:1]=[C:2]1[N:13]2[C:14]3[C:10]([CH:11]=[CH:12]2)=[C:9]([CH:15]=O)[CH:8]=[CH:7][C:6]=3[CH2:5][NH:4][CH2:3]1.[CH3:17][O:18][NH2:19].Cl>CCO.N1C=CC=CC=1>[CH3:17][O:18][N:19]=[CH:15][C:9]1[CH:8]=[CH:7][C:6]2[CH2:5][NH:4][CH2:3][C:2](=[O:1])[N:13]3[C:14]=2[C:10]=1[CH:11]=[CH:12]3

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4113O-MethylhydroxylamineHCID 86758916HCID 86758916, compound

Product 1

HCID 131723851HCID 131723851, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1049PyridineSolvent

Procedure

A solution of 1-oxo-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indole-7-carbaldehyde (Example 45, 0.050 g, 0.234 mmol) and MeONH2. HCl (0.020 g, 0.242 mmol) in EtOH (5 mL) and pyridine (5 mL) was refluxed for 20 h. The reaction mixture was then evaporated to dryness and the residue was taken up in H2O and extracted with EtOAc several times. The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by flash silica gel chromatography eluting with a gradient of 0-1% MeOH in CHCl3 to give 0.036 g (63%) of the (E) and 0.013 g (23%) of the (Z) isomers. (Z) isomer: 1H NMR (DMSO-d6) δ 3.54-3.58 (m, 2H), 3.96 (s, 3H), 4.43 (bs, 2H), 7.27 (t, 1H, J=9.0 Hz), 7.89-7.92 (m, 2H), 8.14 (d, 1H, J=9.0 Hz), 8.21 (s, 1H), 8.35-8.39 (m, 1H). HRMS calcd for C13H13N3O2 (M+) 243.1008, found 243.1020. Anal. (C13H13N3O2.0.1 H2O.0.1 EtOAc) C, H, N. (E) isomer: 1H NMR (DMSO-d6) δ 3.55 (bs, 2H), 3.87 (s, 3H), 4.37 (bs, 2H), 7.27 (t, 1H, J=7.5 Hz), 7.75 (s, 1H), 7.91 (d, 1H, J=7.5 Hz), 8.24 (d, 1H, J=7.5 Hz), 8.34-8.38 (m, 2H). HRMS calcd. for C13H13N3O2 (M+) 243.1008, found 243.1016. Anal. (C13H13N3O2.0.25 H2O) C, H, N.

Workup

  1. customThe reaction mixture was then evaporated to dryness
  2. extractionextracted with EtOAc several times
  3. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash silica gel chromatography
  7. washeluting with a gradient of 0-1% MeOH in CHCl3

Sources & evidence

ORD record
ord-3f6c296aef81455ead9773c2d131cc5e
Source dataset
uspto-grants-2003_04
Patent number
US06548494B1

Reaction notes

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