Tetrahydrofuran → HCID 86713578, compound

HRID 524054Notes

Reaction equation

HRID 524054 reaction equation
COC1[CH:4]=[C:5]([NH:11][CH2:12][C:13]2[C:14]([NH:21][CH3:22])=[N:15][C:16]([S:19][CH3:20])=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(N(C(C)C)C(C)C)C.ClC(Cl)(O[C:36](=O)[O:37][C:38](Cl)(Cl)Cl)Cl.C1C[O:47][CH2:46]C1>>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([N:11]2[CH2:12][C:13]3[C:14](=[N:15][C:16]([S:19][CH3:20])=[N:17][CH:18]=3)[N:21]([CH3:22])[C:46]2=[O:47])[CH:4]=[C:36]([O:37][CH3:38])[CH:8]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 86713577HCID 86713577, compound

Product 1

HCID 86713578HCID 86713578, compound

Procedure

To a mixture of 5-((3,5-dimethoxyphenylamino)methyl)-N-methyl-2-(methylthio)pyrimidin-4-amine (1.1 g, 3.43 mmol) and N-ethyl-N-isopropylpropan-2-amine (1.33 g, 10.30 mmol) in 10 mL of THF was added a solution of triphosgene (357 mg, 1.20 mmol) in 5 mL of THF at 0° C., and stirred for 1 h. The reaction mixture was then warmed to RT and stirred for another 5 h. LCMS showed the reaction was completed. The reaction mixture was quenched by water and extracted with ethyl acetate (3×15 mL). The organic layers were separated, combined, washed with saturated aqueous solution of sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated to afford the title compound (crude 1.1 g, 92%) as a white solid, which was directly used in the next step without further purification. MS (ES+) C16H18N4O3S requires: 346. found: 347 [M+H]+.

Workup

  1. stirringstirred for another 5 h
  2. customThe reaction mixture was quenched by water
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. customThe organic layers were separated
  5. washwashed with saturated aqueous solution of sodium bicarbonate and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-2888a4cc569e42c0b335233d398ee593
Source dataset
uspto-grants-2016_05
Patent number
US09340514B2

Reaction notes

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