Diisopropylethylamine → 2-Methoxy-N-(6-(4-nitronaphthalen-1-yloxy)pyrimidin-4-yl)acetamide

HRID 2069143Notes

Reaction equation

HRID 2069143 reaction equation
[N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][C:15]2[N:20]=[CH:19][N:18]=[C:17]([NH2:21])[CH:16]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].CCN(C(C)C)C(C)C.[CH3:31][O:32][CH2:33][C:34](Cl)=[O:35]>C(Cl)Cl>[CH3:31][O:32][CH2:33][C:34]([NH:21][C:17]1[CH:16]=[C:15]([O:14][C:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[N:20]=[CH:19][N:18]=1)=[O:35]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 585325356-(4-Nitronaphthalen-1-yloxy)pyrimidin-4-amine

Product 1

HCID 708814402-Methoxy-N-(6-(4-nitronaphthalen-1-yloxy)pyrimidin-4-yl)acetamideYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 6-(4-nitronaphthalen-1-yloxy)pyrimidin-4-amine (350 mg, 1.24 mmol) in DCM (10.0 mL) and DIPEA (433 μL, 2.48 mmol) at 0° C. was added 2-methoxyacetyl chloride (170 μL, 1.860 mmol). The mixture was warmed to RT and after 3 hr the reaction was quenched by the addition of a solution of NH3 in MeOH (7M, 20 mL) and after a further 10 min was evaporated in vacuo. The residue was partitioned between DCM (30 mL) and saturated aq NaHCO3 solution (30 mL) and the organic layer was separated and washed with brine (30 mL) and then dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, MeOH in DCM, 0-100%, gradient elution) to furnish the title compound as a yellow solid (400 mg, 86%); Rt 4.60 min (Method 1 basic); m/z 355 (M+H)+ (ES+).

Workup

  1. customwas quenched by the addition of a solution of NH3 in MeOH (7M, 20 mL) and after a further 10 min
  2. customwas evaporated in vacuo
  3. customThe residue was partitioned between DCM (30 mL) and saturated aq NaHCO3 solution (30 mL)
  4. customthe organic layer was separated
  5. washwashed with brine (30 mL)
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, 40 g, MeOH in DCM, 0-100%, gradient elution)

Sources & evidence

ORD record
ord-6befa2ee158b4bfa8f6891c9c2ae10dd
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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