Toluene → 6-Methyl-5-[4-(methylamino)phenyl]thieno[2,3-d]pyrimidin-4-amine

HRID 227625Notes

Reaction equation

HRID 227625 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:15]([NH2:17])=[N:14][CH:13]=[N:12][C:11]=3[S:10][C:9]=2[CH3:18])=[CH:4][CH:3]=1.[C:19](OC=O)(=O)C.COCCO[AlH2-]OCCOC.[Na+].C1(C)C=CC=CC=1>ClCCl.C1COCC1>[CH3:18][C:9]1[S:10][C:11]2[N:12]=[CH:13][N:14]=[C:15]([NH2:17])[C:16]=2[C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([NH:1][CH3:19])=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 75269Acetic-formic anhydrideHCID 65399685-(4-Aminophenyl)-6-methylthieno[2,3-d]pyrimidin-4-amineHCID 16684438Red-Al

Product 1

HCID 116946866-Methyl-5-[4-(methylamino)phenyl]thieno[2,3-d]pyrimidin-4-amineYield 20.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A −20° C. suspension of Example 1E (400 mg, 1.56 mmol) in dichloromethane (10 mL) and THF (10 mL) was treated with formic acetic anhydride (0.135 mL, 1.7 mmol), stirred for 1 hour, and concentrated. The concentrate was suspended in benzene (50 mL), treated with 65% Red-Al in toluene (2.4 mL, 7.8 mmol), stirred at room temperature for 20 minutes than heated to reflux for 6 hours. The reaction was cooled to room temperature and partitioned between Rochelle's salt and ethyl acetate. The aqueous phase was extracted three times with ethyl acetate and the combined extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 7% methanol/dichloromethane to provide the desired product (86 mg). MS(ESI(+)) m/e 271 (M+H)+.

Workup

  1. concentrationconcentrated
  2. stirringstirred at room temperature for 20 minutes
  3. temperaturethan heated
  4. temperatureto reflux for 6 hours
  5. custompartitioned between Rochelle's salt and ethyl acetate
  6. extractionThe aqueous phase was extracted three times with ethyl acetate
  7. washthe combined extracts were washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe concentrate was purified by flash column chromatography on silica gel with 7% methanol/dichloromethane

Sources & evidence

ORD record
ord-60b3bca3699f41fdb87cc4fb06093759
Source dataset
uspto-grants-2009_07
Patent number
US07560552B2

Reaction notes

Loading…