1,2-Dichloroethane → HCID 86711376, compound

HRID 532928Notes

Reaction equation

HRID 532928 reaction equation
[F:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:17]3[CH2:16][CH2:15][N:14]4[C:18](=[O:24])[CH2:19][NH:20][C:21](=O)[CH:22]=[C:13]4[C:12]=3[N:11]=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.ClCCCl.[CH:29]([C:32]1[N:33]=[CH:34][NH:35][CH:36]=1)([CH3:31])[CH3:30].C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:17]3[CH2:16][CH2:15][N:14]4[C:18](=[O:24])[CH2:19][N:20]=[C:21]([N:35]5[CH:36]=[C:32]([CH:29]([CH3:31])[CH3:30])[N:33]=[CH:34]5)[CH:22]=[C:13]4[C:12]=3[N:11]=[CH:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 516892Sodium BicarbonateHCID 86711375HCID 86711375, compoundHCID 178439626HCID 178439626, compound

Product 1

HCID 86711376HCID 86711376, compoundYield 27.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

EXAMPLE 94. To a stirred solution of 4-(6-fluoropyridin-3-yl)-5,6,9,10-tetrahydro-[1,4]diazepino[1,7-h][1,7]naphthyridine-8,11-dione (31 mg, 0.096 mmol) in 1,2-dichloroethane (2 mL) POCl3 (29.3 mg, 0.19 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 (5 mL), 4-isopropyl-1H-imidazole (53 mg, 0.48 mmol) was added and the mixture was stirred at 100° C. for 1 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: DEAP 5 μm, 250×30 mm, 60A, Princeton; eluent: from 6% MeOH/CO2 to 11% MeOH/CO2 in 11 min; flow 100 mL/min; UV detection at 220 nm) and yielded the title compound as beige powder (11 mg). UPLC-MS: MS 417.2 (M+H+); UPLC rt 0.87 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.17-1.34 (m, 6 H), 2.81-2.98 (m, 3 H), 4.05 (br. s., 2 H), 4.40 (s, 2 H), 7.09 (dd, J=8.3, 2.8 Hz, 1 H), 7.22-7.36 (m, 2 H), 7.77 (td, J=7.9, 2.1 Hz, 1 H), 7.96 (s, 1 H), 8.03 (s, 1 H), 8.23 (d, J=1.5 Hz, 1 H), 8.68 (d, J=4.8 Hz, 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 (5 mL)
  7. stirringthe mixture was stirred at 100° C. for 1 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: DEAP 5 μm, 250×30 mm, 60A, Princeton; eluent: from 6% MeOH/CO2 to 11% MeOH/CO2 in 11 min; flow 100 mL/min; UV detection at 220 nm)

Sources & evidence

ORD record
ord-2631358584864ef0a48fdd47975b6ec0
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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