Hydrochloric Acid → HCID 58213571, compound

HRID 340284Notes

Reaction equation

HRID 340284 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:18](OCC)=[O:19])=[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.C([BH-](CC)CC)C.[Li+].Cl.C(=O)(O)[O-].[Na+]>C1COCC1>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:15]=[CH:16][C:17]([CH2:18][OH:19])=[CH:23][CH:24]=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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 23664628LithiumtriethylborohydrideHCID 58213536HCID 58213536, compound

Product 1

HCID 58213571HCID 58213571, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)benzoate (Example 70) (1.0 eq.) in THF (0.1 M) at 0° C. was added 1.0 M lithium triethylborohydride in THF (10 eq.) and warmed to room temperature over 2 hours. 1N HCl aqueous solution was added slowly to quench the reaction, and the mixture was heated to reflux for 30 minutes. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate solution. The two phases were separated, and the aqueous layer was extracted with ethyl acetate (EA). 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 (4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)phenyl)methanol. 1H NMR (Acetone-d6): δ 8.77 (s, 1H), 8.69 (s, 1H), 8.26 (d, 1H), 7.40 (s, 1H), 7.21-7.28 (m, 4H), 7.13 (d, 1H), 6.5 (br, 2H), 4.56 (s, 2H), 4.1 (br t, 1H), 3.10-3.23 (m, 4H), 2.44 (s, 3H). LRMS [M+H]=344.2

Workup

  1. customto quench
  2. customthe reaction
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 30 minutes
  5. customThe two phases were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (EA)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous MgSO4
  9. concentrationconcentrated en vacuo
  10. customThe crude material was purified by RP-HPLC
  11. extractionfollowed by extraction in DCM

Sources & evidence

ORD record
ord-9b60801adeed453ea8e2416cf5d6159c
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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