Diethyl Ether → HCID 49838131, compound

HRID 1259161Notes

Reaction equation

HRID 1259161 reaction equation
[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:24]=[CH:23][C:17](C(OCC)=O)=[CH:16][C:15]=3[CH3:25])=[CH:7][C:6]=2[C:5]2[CH:26]=[CH:27][C:28]([CH3:30])=[CH:29][C:4]=2[N:3]=1.[CH3:31][Mg]I.CC[O:36][CH2:37][CH3:38]>C(Cl)Cl>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:24]=[CH:23][C:17]([C:37]([OH:36])([CH3:38])[CH3:31])=[CH:16][C:15]=3[CH3:25])=[CH:7][C:6]=2[C:5]2[CH:26]=[CH:27][C:28]([CH3:30])=[CH:29][C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 53339050HCID 53339050, compoundHCID 178418373HCID 178418373, compound

Product 1

HCID 49838131HCID 49838131, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl 4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylbenzoate (from Example 74) (1.0 eq.) in DCM at 0° C. was added 3.0 M methyl magnesium iodide (10 eq.) in ether and warmed to room temperature overnight. The reaction was cooled to 0° C. and quenched with water. After stirring for 15 min, the reaction mixture was neutralized with saturated aqueous sodium bicarbonate solution and added EA. The two phases were separated, and the aqueous layer was extracted three times with EA. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% MeOH in DCM to give a 2-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenyl)propan-2-ol. 1H NMR (Acetone-d6): δ 8.72-8.75 (m, 2H), 8.23 (d, 1H), 7.41 (s, 1H), 7.32 (s, 1H), 7.25 (d, 1H), 7.12-7.14 (m, 2H), 6.6 (br, 2H), 3.91 (s, 1H), 3.07-3.18 (m, 4H), 2.44 (s, 3H), 2.31 (s, 3H), 1.48 (s, 6H). LRMS [M+H]=386.2

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customquenched with water
  3. additionadded EA
  4. customThe two phases were separated
  5. extractionthe aqueous layer was extracted three times with EA
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. concentrationconcentrated en vaccuo
  9. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-8cdea09d93c44d4a87efd83c26333a05
Source dataset
uspto-grants-2013_06
Patent number
US08466167B2

Reaction notes

Loading…