Azobisisobutyronitrile → HCID 66779869, compound

HRID 1958058Notes

Reaction equation

HRID 1958058 reaction equation
[Cl:1][C:2]1[C:3]([CH3:26])=[C:4]([CH2:8][N:9]2[C:14]3[N:15]=[C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[S:17][C:13]=3[C:12](=[O:24])[N:11]=[C:10]2[CH3:25])[CH:5]=[CH:6][CH:7]=1.[Br:27]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>O1CCCC1.O>[Br:27][CH2:25][C:10]1[N:9]([CH2:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[CH3:26])[C:14]2[N:15]=[C:16]([N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[S:17][C:13]=2[C:12](=[O:24])[N:11]=1

Participants

6

Reactant 3

HCID 6547AzobisisobutyronitrileHCID 67184N-bromobutanimideHCID 66779813HCID 66779813, compound

Product 1

HCID 66779869HCID 66779869, compoundYield 62.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 40 mL I-CHEM reaction vial equipped with a stirbar, was added Example 60, 4-[(3-chloro-2-methylphenyl)methyl]-5-methyl-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (1 g, 2.56 mmol), N-bromosuccinimide (0.569 g, 3.20 mmol), and 2,2′-azobis(2-methylpropionitrile) (0.084 g, 0.512 mmol). The solids were taken up in tetrahydrofuran (THF) (25.6 ml) and stirred overnight at room temperature. After overnight stirring, the reaction was diluted with water (˜10 mL) transferred to a separatory funnel and extracted with dichloromethane DCM (˜50 mL). The organic layer was dried over sodium sulfate and concentrated to a residue. The residue was re-dissolved in a minimum amount of DCM (˜2 mL) and injected onto a 25 g SNAP silica cartridge for purification (eluting with a gradient: 5%-75% THF (1% methanol (MeOH)) into DCM, over 30 column volumes). Fractions containing the desired material were pooled and concentrated to afford 5-(bromomethyl)-4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (752 mg, 1.601 mmol, 62.6% yield). LC/MS Theoretical m/z MH+=470.78 Found: 470.8; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.45 (s, 3H) 3.46-3.56 (m, 4H) 3.66 (t, J=4.93 Hz, 5H) 4.46 (s, 2H) 5.58 (s, 2H) 6.53 (d, J=8.08 Hz, 1H) 7.14 (t, J=7.96 Hz, 1H) 7.37 (d, J=7.83 Hz, 1H).

Workup

  1. customTo a 40 mL I-CHEM reaction
  2. customvial equipped with a stirbar
  3. stirringAfter overnight stirring
  4. customtransferred to a separatory funnel
  5. extractionextracted with dichloromethane DCM (˜50 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated to a residue
  8. dissolutionThe residue was re-dissolved in a minimum amount of DCM (˜2 mL)
  9. custominjected onto a 25 g SNAP silica cartridge for purification (
  10. washeluting with a gradient
  11. additionFractions containing the desired material
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-93d7b4cbc94649df876fbac1b0a2759c
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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