Dimethylamine → HCID 10001523, compound

HRID 645919Notes

Reaction equation

HRID 645919 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:27])[NH:10][C:11](=[O:26])[C:12]=1[C:13]1[C:21]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[N:15]([CH2:22][CH2:23][CH2:24]O)[CH:14]=1.[N:28]1[CH:33]=CC=C[CH:29]=1.CS(OS(C)(=O)=O)(=O)=O.CNC>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:27])[NH:10][C:11](=[O:26])[C:12]=1[C:13]1[C:21]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[N:15]([CH2:22][CH2:23][CH2:24][N:28]([CH3:33])[CH3:29])[CH:14]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 1049PyridineHCID 81560Methanesulfonic anhydrideHCID 9977154HCID 9977154, compound

Product 1

HCID 10001523HCID 10001523, compoundYield 31.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of Compound 1 (45 mg, 0.118 mmol) in THF (5 mL) was added pyridine (41 mg, 0.5 mmol). The mixture was stirred at room temperature for 15 min and then methanesulfonic anhydride (65 mg, 0.37 mmol) was added and the mixture was heated to 50° C. for 2 h. TLC and mass spectra showed the formation of Compound 2a. To the crude product was added excess 1.0 M solution of dimethylamine in THF (1 mL). The mixture was heated from 50 to 65° C. overnight. The solvent was concentrated in vacuo. The crude product was extracted with ethyl acetate (100 mL). The organic phase was washed with saturated NaHCO3, brine, and evaporated in vacuo to give a crude product (50 mg). The crude product was separated by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, from 98:2:0.2 to 95:5:0.5) to give 15 mg (31%) of Compound 2 as a yellow solid. 1H NMR (DMSO-d6) δ 8.27 (s, 1H), 8.23 (m, 1H), 7.44-7.33 (m, 4H), 6.75-6.71 (m, 1H), 6.62-6.60 (m, 1H), 4.41-4.38 (m, 2H), 2.3-2.28 (m, 2H), 2.25 (s, 6H), 2.12-2.05 (m, 2H). ES-MS m/z 409 (MH+).

Workup

  1. temperaturethe mixture was heated to 50° C. for 2 h
  2. temperatureThe mixture was heated from 50 to 65° C. overnight
  3. concentrationThe solvent was concentrated in vacuo
  4. extractionThe crude product was extracted with ethyl acetate (100 mL)
  5. washThe organic phase was washed with saturated NaHCO3, brine
  6. customevaporated in vacuo
  7. customto give a crude product (50 mg)
  8. customThe crude product was separated by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, from 98:2:0.2 to 95:5:0.5)

Sources & evidence

ORD record
ord-3d44ba12dbe149c69960f0007049fbe2
Source dataset
uspto-grants-2010_04
Patent number
US07705015B2

Reaction notes

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