HCID 59436032, compound → HCID 25226757, compound

HRID 1802485Notes

Reaction equation

HRID 1802485 reaction equation
[C:1]([C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([NH:11][C:12]2[C:21]3[CH:20]=[CH:19][NH:18][C:17](=[O:22])[C:16]=3[C:15]3[CH:23]=[C:24]([C:27]4[N:28]=[C:29]([C:32]([OH:35])([CH3:34])[CH3:33])[S:30][CH:31]=4)[CH:25]=[CH:26][C:14]=3[N:13]=2)=[C:6]([Cl:36])[CH:5]=1)(=[O:3])[CH3:2].[CH3:37][Mg]Br>C1COCC1>[Cl:36][C:6]1[CH:5]=[C:4]([C:1]([OH:3])([CH3:37])[CH3:2])[CH:9]=[C:8]([Cl:10])[C:7]=1[NH:11][C:12]1[C:21]2[CH:20]=[CH:19][NH:18][C:17](=[O:22])[C:16]=2[C:15]2[CH:23]=[C:24]([C:27]3[N:28]=[C:29]([C:32]([OH:35])([CH3:33])[CH3:34])[S:30][CH:31]=3)[CH:25]=[CH:26][C:14]=2[N:13]=1

Participants

4

Reactant 2

HCID 59436032HCID 59436032, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 25226757HCID 25226757, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-[(4-acetyl-2,6-dichlorophenyl)amino]-9-[2-(1-hydroxy-1-methylethyl)-1,3-thiazol-4-yl]benzo[c]-2,6-naphthyridin-1(2H)-one (75 mg, 0.14 mmol) in THF (2 mL) was cooled to −10° C. and methyl magnesium bromide (0.79 mL, 1.11 mmol, 1.4 M in toluene/THF) was added. The reaction was stirred rapidly keeping the temperature between −5 & 0° C. for 1 h. After warming to room temperature, the reaction was quenched with water, diluted with ethyl acetate/THF (1:3), and extracted with water. The organic layer was dried with sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with methanol in dichloromethane followed by reverse phase HPLC to afford the title compound.

Workup

  1. custombetween −5 & 0° C.
  2. customfor 1 h
  3. customthe reaction was quenched with water
  4. additiondiluted with ethyl acetate/THF (1:3)
  5. extractionextracted with water
  6. dry with materialThe organic layer was dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel eluting with methanol in dichloromethane

Sources & evidence

ORD record
ord-5543f37510c648a1a2744fd9f4bf84bc
Source dataset
uspto-grants-2013_01
Patent number
US08349865B2

Reaction notes

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