1,2-Dichloroethane → HCID 73335918, compound

HRID 532938Notes

Reaction equation

HRID 532938 reaction equation
[S:1]1[CH:5]=[C:4]([C:6]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:7]=2[CH2:8][CH2:9][N:10]2[C:20](=[O:21])[CH2:19][NH:18][C:17](=O)[CH:16]=[C:11]23)[N:3]=[CH:2]1.ClCCCl.[CH3:27][O:28][CH2:29][C:30]1[N:31]=[CH:32][NH:33][CH:34]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:27][O:28][CH2:29][C:30]1[N:31]=[CH:32][N:33]([C:17]2[CH:16]=[C:11]3[C:12]4[C:7]([CH2:8][CH2:9][N:10]3[C:20](=[O:21])[CH2:19][N:18]=2)=[C:6]([C:4]2[N:3]=[CH:2][S:1][CH:5]=2)[CH:15]=[CH:14][CH:13]=4)[CH:34]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 516892Sodium BicarbonateHCID 86711382HCID 86711382, compoundHCID 178494610HCID 178494610, compound

Product 1

HCID 73335918HCID 73335918, compoundYield 13.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Example 101. To a stirred solution of 9-(thiazol-4-yl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (160 mg, 0.51 mmol) in 1,2-dichloroethane (4 mL) POCl3 (0.096 mL, 1.03 mmol) was added and the resulting suspension was stirred at 100° C. for 1 h. The reaction mixture was cooled to rt and concentrated under reduced pressure to dryness. For complete removal of POCl3 the residue was taken up in toluene and evaporated twice again and dried under high vacuo. The resulting crude chloro compound was dissolved in 1,2-dichloroethane (4 mL), 4-(methoxymethyl)-1H-imidazole (172 mg, 1.53 mmol) was added and the mixture was stirred at 100° C. for 2 h. The reaction mixture was allowed to warm to rt and diluted with DCM. Saturated aqueous NaHCO3 solution was added and the mixture was extracted twice with DCM. The combined organic layers were dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The crude product was purified by SFC (column: Reprosil 70 NH2, 5 μm, 250×30 mm, Dr. Maisch; eluent: 14% MeOH/CO2 for 1 min, then from 14% MeOH/CO2 to 19% MeOH/CO2 in 6 min; flow 100 mL/min; UV detection at 220 nm) to yield the title compound as white powder (27 mg). UPLC-MS: MS 406.2 (M+H+); UPLC rt 0.78 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.14 (t, J=5.9 Hz, 2 H), 3.42 (s, 3 H), 3.85 (t, J=6.1 Hz, 2 H), 4.39 (br. s., 2 H), 4.44 (s, 2 H), 6.61 (s, 1 H), 7.37-7.50 (m, 3 H), 7.68 (d, J=7.8 Hz, 1 H), 7.72 (d, J=7.8 Hz, 1 H), 8.04 (s, 1 H), 8.95 (s, 1 H).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. concentrationconcentrated under reduced pressure to dryness
  3. customFor complete removal of POCl3 the residue
  4. customevaporated twice again
  5. customdried under high vacuo
  6. dissolutionThe resulting crude chloro compound was dissolved in 1,2-dichloroethane (4 mL)
  7. stirringthe mixture was stirred at 100° C. for 2 h
  8. temperatureto warm to rt
  9. extractionthe mixture was extracted twice with DCM
  10. dry with materialThe combined organic layers were dried with sodium sulfate
  11. filtrationfiltered
  12. customthe solvent was removed under reduced pressure
  13. customThe crude product was purified by SFC (column
  14. waiteluent: 14% MeOH/CO2 for 1 min
  15. waitfrom 14% MeOH/CO2 to 19% MeOH/CO2 in 6 min

Sources & evidence

ORD record
ord-f8c14f374fc24b7c88c9af03a27b5c43
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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