Dimethylamine → HCID 10002471, compound

HRID 2112804Notes

Reaction equation

HRID 2112804 reaction equation
O[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[C:15](=[O:30])[NH:16][C:17](=[O:29])[C:18]=2[C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)=[CH:6]1.[N:31]1[CH:36]=CC=C[CH:32]=1.CS(OS(C)(=O)=O)(=O)=O.CNC>C1COCC1>[CH3:32][N:31]([CH3:36])[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[C:15](=[O:30])[NH:16][C:17](=[O:29])[C:18]=2[C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)=[CH:6]1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 1049PyridineHCID 81560Methanesulfonic anhydrideHCID 10000872HCID 10000872, compound

Product 1

HCID 10002471HCID 10002471, compoundYield 22.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of Compound 3 (25 mg, 0.063 mmol) in THF (5 mL) was added pyridine (24.9 mg, 0.315 mmol). The mixture was stirred at room temperature for 15 min and then methanesulfonic anhydride (43.9 mg, 0.25 mmol) was added and the mixture was heated to 50° C. for 2 h. TLC and mass spectra shown the formation of Compound 4a. 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 6 mg (22%) of Compound 4 as a yellow solid. 1H NMR (CDCl3) δ 8.33 (s, 1H), 8.08 (dd, J=1.5, 4.7 Hz, 1H), 7.94 (m, 1H), 7.86 (d, J=8.2 Hz, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.54 (m, 2H), 7.41 (t, J=6.9 Hz, 1H), 7.28 (m, 1H), 6.44 (dd, J=4.7, 8.1 Hz, 1H), 6.26 (dd, J=1.5, 8.0 Hz, 1H), 4.37 (t, J=7.1 Hz, 2H), 2.29 (t, J=7.0 Hz, 2H), 2.25 (s, 6H), 2.07 (m, 2H). ES-MS m/z 425 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-34891634d5bb4c838b431fd0a3a12b32
Source dataset
uspto-grants-2009_04
Patent number
US07524858B2

Reaction notes

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