Hydrochloric Acid → HCID 178464391, compound

HRID 424559Notes

Reaction equation

HRID 424559 reaction equation
[CH2:1]([N:3]([CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][S:16][C:15]2[CH:19]=[CH:20][C:21]([NH:23][C:24]([C:26]3[S:27][CH:28]=[CH:29][CH:30]=3)=[NH:25])=[CH:22][C:14]1=2)C(=O)OC(C)(C)C)[CH3:2].Cl>CO>[CH2:1]([NH:3][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][S:16][C:15]2[CH:19]=[CH:20][C:21]([NH:23][C:24]([C:26]3[S:27][CH:28]=[CH:29][CH:30]=3)=[NH:25])=[CH:22][C:14]1=2)[CH3:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 178464393HCID 178464393, compound

Product 1

HCID 178464391HCID 178464391, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred suspension of tert-butyl ethyl(2-(6-(thiophene-2-carboximidamido)-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)carbamate (410 mg, 0.918 mmol) in methanol (6 mL) was added a 3N HCl solution (3.06 mL, 9.18 mmol). The resulting mixture was stirred at 90° C. for 30 minutes The mixture was then passed through a 0.45 μM syringe filter, and the filtrate was concentrated in vacuo to dry foam. The residue was then partitioned between 1:1 water:saturated sodium carbonate and dichloromethane. The organic layer was separated, and the aqueous phase was extracted again with dichloromethane. The organic phase was dried, filtered, concentrated, and then chromatographed in 1:4:5 (2M NH3 in methanol):ethyl acetate:dichloromethane giving the desired product 24 (135 mg, 42.4%). 1H NMR (DMSO-d6) δ 7.71 (d, J=3.6 Hz, 1H), 7.58 (d, 5.1 Hz, 1H), 7.08 (t, J=4.4 Hz, 1H), 6.82 (d, J=7.8 Hz, 1H), 6.33 (brs, 2H), 6.21 (s, 1H), 6.07 (dd, J=8.1, 1.5 Hz, 1H), 3.63-3.57 (m, 2H), 3.33-3.28 (m, 2H), 3.01-2.96 (m, 2H), 2.71-2.65 (m, 2H), 2.53 (q, J=7.0 Hz, 2H), 1.66 (brs, 1H), 1.17 (t, J=7.0 Hz, 3H); ESI-MS (m/z, %): 347 (MH+, 83), 276 (100); HRMS calculated for C17H23N4S2 (MH+), calculated: 347.1358, observed: 347.1346; HPLC purity: 97% by area.

Workup

  1. customwas then passed through a 0.45 μM syringe
  2. filtrationfilter
  3. concentrationthe filtrate was concentrated in vacuo
  4. customto dry foam
  5. customThe residue was then partitioned between 1:1 water
  6. customThe organic layer was separated
  7. extractionthe aqueous phase was extracted again with dichloromethane
  8. customThe organic phase was dried
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customchromatographed in 1:4:5 (2M NH3 in methanol)

Sources & evidence

ORD record
ord-31cd129d9fec4c74aa8dc7c0357d5691
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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