4-Aminopyrimidine → HCID 86687725, compound

HRID 1473652Notes

Reaction equation

HRID 1473652 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:34][CH3:35])=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([O:21]C4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=O)=[CH:15][CH:16]=3)[C:11](=[O:33])[NH:10][N:9]=2)[CH:7]=1.[N:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[N:38][CH:37]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:34][CH3:35])=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:42][C:39]4[CH:40]=[CH:41][N:36]=[CH:37][N:38]=4)(=[O:21])=[O:20])=[CH:15][CH:16]=3)[C:11](=[O:33])[NH:10][N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 689584-AminopyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 86687720HCID 86687720, compound

Product 1

HCID 86687725HCID 86687725, compoundYield 25.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A vial was charged with perfluorophenyl 1-(5-chloro-2-methoxyphenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonate (From Step 6, Example 501; 126 mg, 0.236 mmol), pyrimidin-4-amine (33.7 mg, 0.355 mmol), and THF (1.18 mL). The resulting solution was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (591 μl, 0.591 mmol) was added drop wise. LCMS after 2 h showed complete conversion of SM to product. The reaction was quenched with 1 mL of MeOH. Purification was done via RPLC with 0.1% NH4OH in ACN and water as mobile phase to afford 1-(5-chloro-2-methoxyphenyl)-4-oxo-N-(pyrimidin-4-yl)-3,4-dihydrophthalazine-6-sulfonamide (27 mg, 25.7% yield). m/z (ESI) 444.0 (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. customPurification

Sources & evidence

ORD record
ord-096df1436d1c43a6925e11941e20c960
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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