Hydrochloric Acid → (S)-8-((2-amino-4-methylpentyl)oxy)-6-(cyclopropylmethyl)benzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398322Notes

Reaction equation

HRID 1398322 reaction equation
[CH:1]1([CH2:4][N:5]2[C:14]3[CH:15]=[C:16]([O:19][CH2:20][C@@H:21]([NH:26]C(=O)OC(C)(C)C)[CH2:22][CH:23]([CH3:25])[CH3:24])[CH:17]=[CH:18][C:13]=3[C:12]3[C:7](=[CH:8][N:9]=[CH:10][CH:11]=3)[C:6]2=[O:34])[CH2:3][CH2:2]1.Cl.O1CCOCC1>CO>[NH2:26][C@@H:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:20][O:19][C:16]1[CH:17]=[CH:18][C:13]2[C:12]3[C:7](=[CH:8][N:9]=[CH:10][CH:11]=3)[C:6](=[O:34])[N:5]([CH2:4][CH:1]3[CH2:3][CH2:2]3)[C:14]=2[CH:15]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710326(S)-tert-butyl (1-((6-(cyclopropylmethyl)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213796(S)-8-((2-amino-4-methylpentyl)oxy)-6-(cyclopropylmethyl)benzo[c][2,7]naphthyridin-5(6H)-oneYield 35%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl (1-((6-(cyclopropylmethyl)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.08 g, 0.172 mmol) in anhydrous methanol (5 mL) was added a 4M solution of HCl in 1,4-dioxane (2 mL, 65.8 mmol) dropwise at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was concentrated under reduced pressure to afford crude compound which was purified by preparative HPLC (10 mM ammonium acetate in water:acetonitrile) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-6-(cyclopropylmethyl)benzo[c][2,7]naphthyridin-5(6H)-one (22 mg, 0.060 mmol, 35% yield) as a yellow gum. LC/MS (ESI) m/e 366.2 [(M+H)+, calcd for C22H28N3O2 366.2]; LC/MS retention time (method A): tR=1.47 min; HPLC retention time (method A): tR=9.470 min; HPLC retention time (method B): tR=5.250 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.47 (d, J=0.50 Hz, 1H), 8.78 (d, J=5.77 Hz, 1H), 8.46 (d, J=9.04 Hz, 1H), 8.26 (d, J=5.52 Hz, 1H), 7.28 (d, J=2.26 Hz, 1H), 7.14 (dd, J=9.03, 2.26 Hz, 1H), 4.39 (d, J=6.78 Hz, 2H), 4.31 (dd, J=9.79, 3.76 Hz, 1H), 4.13 (dd, J=9.79, 6.78 Hz, 1H), 3.53 (dd, J=7.15, 3.64 Hz, 1H), 1.87 (m, 1H), 1.59 (q, J=13.72, 7.03 Hz, 2H), 1.36-1.45 (m, 1H), 1.04 (dd, J=7.28, 6.78 Hz, 6H), 0.57-0.63 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto afford crude compound which
  3. customwas purified by preparative HPLC (10 mM ammonium acetate in water:acetonitrile)

Sources & evidence

ORD record
ord-9ae3f8dee66a4c17953a3d3ac2cf8dcd
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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