Tetrabutylammonium Fluoride → (5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)methanol

HRID 2167640Notes

Reaction equation

HRID 2167640 reaction equation
[Si]([O:8][CH2:9][C:10]1[CH:35]=[CH:34][C:13]2=[C:14]3[C:19](=[C:20]([NH2:22])[N:21]=[C:12]2[CH:11]=1)[N:18]=[CH:17][C:16]([CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=1[CH3:33])=[CH:15]3)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH2:22][C:20]1[C:19]2[N:18]=[CH:17][C:16]([CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=3[CH3:33])=[CH:15][C:14]=2[C:13]2[CH:34]=[CH:35][C:10]([CH2:9][OH:8])=[CH:11][C:12]=2[N:21]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 582137038-((Tert-butyldimethylsilyloxy)methyl)-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-5-amine

Product 1

HCID 58166517(5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(Tert-butyldimethylsilyloxy)methyl)-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-5-amine (from step 5) (1.0 equiv.) and TBAF (1.1 equiv.) in THF is stirred at ambient temperature overnight. The reaction is quenched with saturated NaHCO3. The two phases are separated, and the aqueous layer is extracted twice with Et2O. The combined organic layers are washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude material is purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-5% MeOH/DCM to give 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)methanol (2-1) as a white solid. 1H NMR (acetone-d6): δ 8.79 (s, 1H), 8.73 (s, 1H), 8.35 (d, 1H), 7.61 (s, 1H), 7.33 (d, 1H), 7.09 (d, 1H), 6.75 (d, 1H), 6.68 (dd, 1H), 6.57 (br s, 2H), 4.47 (d, 2H), 4.32 (t, 1H), 3.58 (s, 3H), 3.17 (t, 2H), 3.04 (t, 2H), 2.30 (s, 3H). LRMS [M+H]=374.2.

Workup

  1. customThe reaction is quenched with saturated NaHCO3
  2. customThe two phases are separated
  3. extractionthe aqueous layer is extracted twice with Et2O
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material is purified by flash chromatography on a COMBIFLASH® system (ISCO)
  8. customto give 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)methanol (2-1) as a white solid

Sources & evidence

ORD record
ord-2e7f3accbb5c43aa840347574d7dac0b
Source dataset
uspto-grants-2015_06
Patent number
US09045470B2

Reaction notes

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