Dimethylformamide → 3-[2-(5-Chlorothieno[2.3-d]pyrimidin-4-ylamino)ethyl]phenol

HRID 491265Notes

Reaction equation

HRID 491265 reaction equation
CN(C)C=O.Cl[C:7]1[C:8]2[C:15]([Cl:16])=[CH:14][S:13][C:9]=2[N:10]=[CH:11][N:12]=1.Cl.[OH:18][C:19]1[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=1)[CH2:22][CH2:23][NH2:24].C(N(CC)CC)C>C(OCC)(=O)C.O>[Cl:16][C:15]1[C:8]2[C:7]([NH:24][CH2:23][CH2:22][C:21]3[CH:20]=[C:19]([OH:18])[CH:27]=[CH:26][CH:25]=3)=[N:12][CH:11]=[N:10][C:9]=2[S:13][CH:14]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 770013-(2-Aminoethyl)phenol hydrochlorideHCID 157457684,5-Dichlorothieno[2,3-d]pyrimidine

Product 1

HCID 688563303-[2-(5-Chlorothieno[2.3-d]pyrimidin-4-ylamino)ethyl]phenolYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
33 °C

Procedure

Into a 250-mL, 3-necked, round-bottom flask, equipped with a mechanical stirrer, condenser, dropping funnel, and thermocouple temp monitor, under an atmosphere of nitrogen was added N,N-dimethylformamide (75 mL) , 4,5-dichlorothieno[2,3-d]pyrimidine (7.47 g, 36 mmol), 3-hydroxyphenethylamine hydrochloride (5.0 g, 28.8 mmol), and triethylamine (10.7 mmol). After exothermic mixing of the reagents raised the temperature of the reaction mixture to 33° C., the mixture was allowed to stir overnight while returning to 25° C. Then the mixture was poured into water and extracted with warm (60° C.) ethyl acetate (5×70 mL). The combined organic phases were washed with water (2×70 mL), brine (70 mL), dried (MgSO4), filtered through silica gel/Celite plug, and most of the solvent removed in vacuo to give a yellow oil. The oil was dissolved in ethyl acetate (100 mL), heated to reflux, and allowed to cool to 25° C. A yellow crystalline solid formed, and was removed via suction filtration; the product was air dried on the funnel for 3 h, to give 6.34 g, 20.8 mmol, 72 percent yield, 164-165° C.

Workup

  1. customInto a 250-mL, 3-necked, round-bottom flask, equipped with a mechanical stirrer, condenser
  2. additionAfter exothermic mixing of the reagents
  3. customwhile returning to 25° C
  4. extractionextracted
  5. temperaturewith warm (60° C.) ethyl acetate (5×70 mL)
  6. washThe combined organic phases were washed with water (2×70 mL), brine (70 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered through silica gel/Celite plug
  9. custommost of the solvent removed in vacuo
  10. customto give a yellow oil
  11. temperatureheated
  12. temperatureto reflux
  13. temperatureto cool to 25° C
  14. customA yellow crystalline solid formed
  15. customwas removed via suction filtration
  16. customdried on the funnel for 3 h
  17. customto give 6.34 g, 20.8 mmol, 72 percent yield, 164-165° C.

Sources & evidence

ORD record
ord-697c73be89d74b1da17510539aa290e3
Source dataset
uspto-grants-2009_05
Patent number
US07531482B2

Reaction notes

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