Hydrochloric Acid → HCID 73213729, compound

HRID 1398310Notes

Reaction equation

HRID 1398310 reaction equation
[Cl:1][C:2]1[C:7]2[N:8]([CH3:17])[C:9](=[O:16])[C:10]3[C:15]([C:6]=2[CH:5]=[C:4]([Cl:18])[C:3]=1[O:19][CH2:20][C@@H:21]([NH:26]C(=O)OC(C)(C)C)[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:14][CH:13]=[N:12][CH:11]=3.Cl>CO>[NH2:26][C@@H:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:20][O:19][C:3]1[C:4]([Cl:18])=[CH:5][C:6]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[N:8]([CH3:17])[C:7]=2[C:2]=1[Cl:1]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86710317HCID 86710317, compound

Product 1

HCID 73213729HCID 73213729, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl (1-((7,9-dichloro-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.120 g, 0.243 mmol) in anhydrous methanol (5 mL) was added a 4M solution of HCl in 1,4-1,4-dioxane (2 mL, 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 then 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)-7,9-dichloro-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (28 mg, 0.063 mmol, 26% yield) as a yellow solid. LC/MS (ESI) m/e 394.2 [(M+H)+, calcd for C19H22Cl2N3O2 394.1]; LC/MS retention time (method A): tR=1.48 min; HPLC retention time (method A): tR=5.21 min; HPLC retention time (method B): tR=5.73 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.50 (d, J=0.75 Hz, 1H), 8.87 (d, J=5.52 Hz, 1H), 8.58 (s, 1H), 8.32 (d, J=5.27 Hz, 1H), 4.17 (dd, J=9.03, 4.02 Hz, 1H), 4.05 (dd, J=9.03, 7.28 Hz, 1H), 3.93 (s, 3H), 3.37-3.43 (m, 1H), 1.82-1.93 (m, 1H), 1.38-1.57 (m, 2H), 0.99-1.05 (m, 6H).

Workup

  1. concentrationThe reaction mixture was then 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-4227964dc4c248928cbea9ae1878cafe
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

Loading…