4-Aminopyrimidine → HCID 86687728, compound

HRID 1473655Notes

Reaction equation

HRID 1473655 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([O:26]C3C(F)=C(F)C(F)=C(F)C=3F)(=O)=[O:24])=[CH:20][CH:21]=2)[C:16](=[O:38])[NH:15][N:14]=1.[N:39]1[CH:44]=[CH:43][C:42]([NH2:45])=[N:41][CH:40]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:6]=[CH:5][C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([NH:45][C:42]3[CH:43]=[CH:44][N:39]=[CH:40][N:41]=3)(=[O:26])=[O:24])=[CH:20][CH:21]=2)[C:16](=[O:38])[NH:15][N:14]=1

Participants

5

Reactant 3

HCID 689584-AminopyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 86687556HCID 86687556, compound

Product 1

HCID 86687728HCID 86687728, compoundYield 21.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A vial was charged with perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonate (From Step 5, Example 293; 126 mg, 0.222 mmol), pyrimidin-4-amine (31.7 mg, 0.334 mmol), and THF (1.11 mL). The resulting solution was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (489 μl, 0.489 mmol) was added drop wise. LCMS after 15 min showed complete conversion of SM to product. The reaction was quenched with 1 mL of MeOH and concentrated. Purification was done on OJ-H column, with 20% methanol and 0.2% diethylamine. Since the product contained some DEA, it was purified further by mass directed LC purification with TFA to afford 1-(2-methoxy-4-(trifluoromethyl)phenyl)-4-oxo-N-(pyrimidin-4-yl)-3,4-dihydrophthalazine-6-sulfonamide (23 mg, 21.7% yield). m/z (ESI) 478.0 (M+H)+.

Workup

  1. temperatureThe resulting solution was cooled in an ice-water bath for 10 min
  2. customThe reaction was quenched with 1 mL of MeOH
  3. concentrationconcentrated
  4. customPurification
  5. customwas purified further by mass
  6. customLC purification with TFA

Sources & evidence

ORD record
ord-b9b22810cebc4c23b778d046b54c6dd2
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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