Diethyl Ether → HCID 58213693, compound

HRID 340283Notes

Reaction equation

HRID 340283 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][CH:15]=3)=[CH:7][C:6]=2[C:5]2[CH:25]=[CH:26][C:27]([CH3:29])=[CH:28][C:4]=2[N:3]=1.[CH3:30][Mg]I.CC[O:35][CH2:36][CH3:37]>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:36]([OH:35])([CH3:37])[CH3:30])=[CH:16][CH:15]=3)=[CH:7][C:6]=2[C:5]2[CH:25]=[CH:26][C:27]([CH3:29])=[CH:28][C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 58213536HCID 58213536, compoundHCID 178418373HCID 178418373, compound

Product 1

HCID 58213693HCID 58213693, 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)benzoate (from Example 70) (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 1N HCl aqueous solution and ether. After stirring for 15 minutes, the reaction mixture was neutralized with saturated aqueous sodium bicarbonate solution. The two phases were separated, and the aqueous layer was extracted with ether. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by RP-HPLC using a 10-50% MeCN in water gradient followed by extraction in DCM to give 2-(4-(2-(5-amino-8 methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)phenyl)propan-2-ol. 1H NMR (Acetone-d6): δ 8.73 (m, 2H), 8.22 (d, 1H), 7.40-7.44 (m, 3H), 7.20 (d, 2H), 7.12 (d, 1H), 6.5 (br, 2H), 3.94 (s, 1H), 3.21 (t, 2H), 3.08 (t, 2H), 2.44 (s, 3H), 1.47 (s, 6H). LRMS [M+H]=372.2

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customquenched with 1N HCl aqueous solution and ether
  3. customThe two phases were separated
  4. extractionthe aqueous layer was extracted with ether
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated en vacuo
  8. customThe crude material was purified by RP-HPLC
  9. extractionfollowed by extraction in DCM

Sources & evidence

ORD record
ord-27367608769f4f1aa7c5e4ffd6274350
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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