Dimethylformamide → HCID 59004612, compound

HRID 1668442Notes

Reaction equation

HRID 1668442 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)=[CH:7]2)([O-:3])=[O:2].Cl.Cl[CH2:27][CH2:28][CH:29]1[CH2:33][CH2:32][CH2:31][N:30]1[CH3:34].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O.C(OCC)(=O)C>[CH3:34][N:30]1[CH2:31][CH2:32][CH2:33][CH:29]1[CH2:28][CH2:27][N:9]1[C:10]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH:7]=[C:8]1[CH2:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][C:21]([F:24])([F:22])[F:23])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 3017050Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1)HCID 59004647HCID 59004647, compound

Product 1

HCID 59004612HCID 59004612, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

compound 8 (75 mg, 0.223 mmol), 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride (45.2 mg, 0.245 mmol), potassium carbonate (92.4 mg, 0.669 mmol) and anhydrous dimethylformamide (5 mL) were charged to a small, argon purged flask fitted with a magnetic stirbar and resulting solution heated in an oil bath at 65° C. for 20 hours. After cooling to room temperature the mixture was diluted with H2O and ethyl acetate, transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine (twice), dried over magnesium sulphate, filtered and concentrated to afford crude solid. The crude product was purified using dry silica gel column chromatography eluting with 25 mL portions of solvent system (2M NH3 in MeOH:CH2Cl2, 2.5:97.5) to yield a yellow residue, 12 (100 mg, quantitative). 1H NMR (DMSO-d6) δ 1.35-1.45 (m, 2H), 1.58-1.64 (m, 3H), 1.72-1.88 (m, 1H), 1.97-2.05 (m, 2H), 2.08 (s, 3H), 2.86-2.95 (m, 1H), 4.15 (t, 2H, J=7.7 Hz), 4.29 (s, 2H), 6.49 (s, 1H), 7.33-7.43 (m, 4H), 7.57 (d, 1H, J=9.1 Hz), 8.00 (dd, 1H, J=9.1, 2.2 Hz), 8.50 (d, 1H, J=2.2 Hz); ESI-MS (m/z, %): 448 (MH+, 100%).

Workup

  1. customfitted with a magnetic stirbar
  2. customresulting solution
  3. temperatureAfter cooling to room temperature the mixture
  4. customtransferred to a separatory funnel
  5. customthe organic layer collected
  6. extractionThe aqueous layer was further extracted with ethyl acetate
  7. washthe combined organic layers were washed with brine (twice),
  8. dry with materialdried over magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford crude solid
  12. customThe crude product was purified
  13. washeluting with 25 mL portions of solvent system (2M NH3 in MeOH:CH2Cl2, 2.5:97.5)
  14. customto yield a yellow residue, 12 (100 mg, quantitative)

Sources & evidence

ORD record
ord-d0b0e37255674764bdbaddc4eb758d04
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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