Triethylamine → 2-chloro-5,7-dihydro-4-((S)-3-methylmorpholino)thieno[3,4-d]pyrimidine

HRID 595049Notes

Reaction equation

HRID 595049 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:10][S:9][CH2:8][C:6]=2[N:7]=1.CCN(CC)CC.[CH3:19][C@H:20]1[CH2:25][O:24][CH2:23][CH2:22][NH:21]1>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([N:21]2[CH2:22][CH2:23][O:24][CH2:25][C@@H:20]2[CH3:19])[C:5]2[CH2:10][S:9][CH2:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12012220(3S)-3-methylmorpholineHCID 722072892,4-Dichloro-5,7-dihydrothieno[3,4-d]pyrimidine

Product 1

HCID 894875302-chloro-5,7-dihydro-4-((S)-3-methylmorpholino)thieno[3,4-d]pyrimidineYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,4-dichloro-5,7-dihydrothieno[3,4-d]pyrimidine (300 mg, 1.45 mmol) and Et3N (294 mg, 2.9 mmol) in DMF (5.0 mL) at 0° C. was added 3-(S)-methylmorpholine (161 mg, 1.59 mmol) dropwise. After the addition was complete, the mixture was stirred overnight at rt. The solvent was removed under vacuum to give a residue which was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried and concentrated to give the crude product which was purified by preparative TLC (Eluent: petroleum ether/ethyl acetate=2/1) to provide 2-chloro-5,7-dihydro-4-((S)-3-methylmorpholino)thieno[3,4-d]pyrimidine as a light yellow solid (283 mg, 72%).

Workup

  1. additionAfter the addition
  2. customThe solvent was removed under vacuum
  3. customto give a residue which
  4. customwas partitioned between water and ethyl acetate
  5. washThe organic layer was washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customto give the crude product which
  9. customwas purified by preparative TLC (Eluent: petroleum ether/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-2bb5e33fa69c4941ae3eba1445ae4194
Source dataset
uspto-grants-2016_01
Patent number
US09242993B2

Reaction notes

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