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

HRID 1398305Notes

Reaction equation

HRID 1398305 reaction equation
[CH:1]([N:4]1[C:13]2[CH:14]=[C:15]([O:18][CH2:19][C@@H:20]([NH:25]C(=O)OC(C)(C)C)[CH2:21][CH:22]([CH3:24])[CH3:23])[CH:16]=[CH:17][C:12]=2[C:11]2[C:6](=[CH:7][N:8]=[CH:9][CH:10]=2)[C:5]1=[O:33])([CH3:3])[CH3:2].Cl.C(OCC)C>ClCCl>[NH2:25][C@@H:20]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:19][O:18][C:15]1[CH:16]=[CH:17][C:12]2[C:11]3[C:6](=[CH:7][N:8]=[CH:9][CH:10]=3)[C:5](=[O:33])[N:4]([CH:1]([CH3:2])[CH3:3])[C:13]=2[CH:14]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 86710313(S)-tert-butyl (1-((6-isopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213727(S)-8-((2-amino-4-methylpentyl)oxy)-6-isopropylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ((S)-tert-butyl (1-((6-isopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (160 mg, 0.353 mmol) in anhydrous dichloromethane (4 mL) was added a 2 M solution of HCl in diethyl ether (0.88 mL, 1.76 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 product which was purified by preparative HPLC (10 mM ammonium acetate in water; acetonitrile) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-6-isopropylbenzo[c][2,7]naphthyridin-5(6H)-one (45 mg, 0.127 mmol, 36% yield) as an off-white solid. LC/MS (ESI) m/e 354.2 [(M+H)+, calcd for C21H28N3O2 354.2]; LC/MS retention time (method C): tR=1.81 min; HPLC retention time (method A): tR=8.85 min; HPLC retention time (method B): tR=9.50 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.43 (d, J=0.75 Hz, 1H), 8.75 (d, J=5.77 Hz, 1H), 8.42 (d, J=9.04 Hz, 1H), 8.22 (d, J=5.52 Hz, 1H), 7.30 (d, J=2.26 Hz, 1H), 7.10 (dd, J=8.78, 2.26 Hz, 1H), 5.26-5.43 (m, 1H), 4.16 (dd, J=9.16, 3.89 Hz, 1H), 3.98 (dd, J=9.29, 7.03 Hz, 1H), 3.27-3.31 (m, 1H), 1.81-1.92 (m, 1H), 1.73 (d, J=7.03 Hz, 6H), 1.41-1.51 (m, 2H), 1.02 (dd, J=9.54, 6.53 Hz, 6H).

Workup

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

Sources & evidence

ORD record
ord-711a72dd6b2b466398a1df221c4d6c67
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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