Tetrahydrofuran → (2-Methoxy-phenyl)-{4-methyl-3-[3-(2-methylamino-pyrimidin-4-yl)-pyridin-2-yloxy]-phenyl}-methanone

HRID 1361692Notes

Reaction equation

HRID 1361692 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][C:3]=1[O:11][C:12]1[C:17]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH3:25])[N:19]=2)=[CH:16][CH:15]=[CH:14][N:13]=1.C1COCC1.[Br-].[Mg+2].[Br-].[CH3:34][O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[Br-].[Mg+2].[Br-]>C(Cl)Cl>[CH3:34][O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[C:6]([C:5]1[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([O:11][C:12]2[C:17]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH3:25])[N:19]=3)=[CH:16][CH:15]=[CH:14][N:13]=2)[CH:4]=1)=[O:7]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 82241Magnesium BromideHCID 66970597HCID 66970597, compoundHCID 866025964-Methyl-3-[3-(2-methylamino-pyrimidin-4-yl)-pyridin-2-yloxy]-benzoyl chloride

Product 1

HCID 58588533(2-Methoxy-phenyl)-{4-methyl-3-[3-(2-methylamino-pyrimidin-4-yl)-pyridin-2-yloxy]-phenyl}-methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To 4-methyl-3-[3-(2-methylamino-pyrimidin-4-yl)-pyridin-2-yloxy]-benzoyl chloride (50 mg, 0.14 mmol) in a flame dried, round-bottom flask under nitrogen and cooled to −78° C. was added 4 ml of THF, 2 ml methylene chloride and magnesium-bromide-2-methoxy-benzene in THF (0.3 ml, 0.6 mmol). After addition of the magnesium-bromide, the −78° C. dry ice bath was removed and the reaction allowed to warm to room temperature over 4 h. The reaction was quenched with saturated sodium bicarbonate solution and extracted with methylene chloride and brine. The organic layers were combined, dried with sodium sulfate and filtered. The solvent was removed under vacuum and the product was purified via preparative HPLC (Gilson). MS m/z=427 [M+H]+. Calc'd for C25H22N4O3: 426.48.

Workup

  1. customthe −78° C. dry ice bath was removed
  2. temperatureto warm to room temperature over 4 h
  3. customThe reaction was quenched with saturated sodium bicarbonate solution
  4. extractionextracted with methylene chloride and brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed under vacuum
  8. customthe product was purified via preparative HPLC (Gilson)

Sources & evidence

ORD record
ord-837b50f92f14484296ee7f515cc2bff0
Source dataset
uspto-grants-2011_02
Patent number
US07880000B2

Reaction notes

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