Hydrochloric Acid → HCID 71262380, compound

HRID 540142Notes

Reaction equation

HRID 540142 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1.CC1(C)[O:31][CH:30]([CH2:32][NH2:33])[CH2:29][O:28]1.Cl>CO>[O:24]=[S:16]1(=[O:25])[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[CH2:19][N:13]([C:4]2[CH:3]=[C:2]([NH:33][CH2:32][CH:30]([OH:31])[CH2:29][OH:28])[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=3)[N:5]=2)[CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 41223491,3-Dioxolane-4-methanamine, 2,2-dimethyl-HCID 712545984-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Product 1

HCID 71262380HCID 71262380, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (200.0 mg, 0.54 mmol, prepared in analogy to the one in Example 2-1) and 1-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (0.5 mL, 3.8 mmol) was heated with stirring at 160° C. for 16 hours. After being cooled to room temperature, the resulting reaction mixture was diluted with methanol (2.0 mL). Concentrated hydrochloric acid (12.0 N, 0.5 mL) was introduced to the above mixture. The resulting mixture was stirred at room temperature for 1 hour, and then extracted with ethyl acetate (100 mL). The organic layer was washed with brine (50 mL×2), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC to afford 69.2 mg of the product as a white solid (yield was 30%). MS obsd. (ESI+) [(M+H)+] 428, 1H NMR (400 MHz, CD3OD) δ ppm 7.98 (dd, J=7.83, 1.26 Hz, 1 H), 7.89 (d, J=7.33 Hz, 1 H), 7.63 (td, J=7.45, 1.26 Hz, 1 H), 7.57 (s, 1 H), 7.50-7.35 (m, 2 H), 7.29 (dd, J=8.59, 1.77 Hz, 1 H), 6.13 (s, 1 H), 5.14 (s, 2 H), 4.55 (brs, 2 H), 4.04-3.89 (m, 1 H), 3.69 (d, J=5.56 Hz, 2 H), 3.64-3.49 (m, 4 H), 2.41 (s, 3 H).

Workup

  1. temperaturewas heated
  2. temperatureAfter being cooled to room temperature
  3. customthe resulting reaction mixture
  4. stirringThe resulting mixture was stirred at room temperature for 1 hour
  5. extractionextracted with ethyl acetate (100 mL)
  6. washThe organic layer was washed with brine (50 mL×2)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-b7cdf0e59f774f059bc23859d6c7196d
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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