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

HRID 1398309Notes

Reaction equation

HRID 1398309 reaction equation
[CH:1]1([N:4]2[C:13]3[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]=3[C:11]3[C:6](=[CH:7][N:8]=[CH:9][CH:10]=3)[C:5]2=[O:33])[CH2:3][CH2:2]1.Cl.C(OCC)C>ClCCl>[CH2:1]([N:4]1[C:13]2[CH:14]=[C:15]([O:18][CH2:19][C@@H:20]([NH2:25])[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])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 86710316(S)-tert-butyl (1-((6-cyclopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213728(S)-6-allyl-8-((2-amino-4-methylpentyl)oxy)benzo[c][2,7]naphthyridin-5(6H)-oneYield 10,298.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl (1-((6-cyclopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (100 mg, 0.221 mmol) in anhydrous dichloromethane (2 mL) was added a 2 M solution of HCl in diethyl ether (0.176 mL, 0.353 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 (0.1% TFA in water) to afford (S)-6-allyl-8-((2-amino-4-methylpentyl)oxy)benzo[c][2,7]naphthyridin-5(6H)-one (8 mg, 22.76 mmol, 10% yield) as a yellow solid. LC/MS (ESI) m/e 352.2 [(M+H)+, calcd for C21H26N3O2 352.2]; LC/MS retention time (method C): tR=1.80 min; HPLC retention time (method A): tR=8.06 min; HPLC retention time (method B): tR=9.21 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.56 (s, 1H), 8.85 (d, J=6.27 Hz, 1H), 8.55 (d, J=9.04 Hz, 1H), 8.48 (d, J=6.27 Hz, 1H), 7.20 (dd, J=8.91, 2.38 Hz, 1H), 7.14 (d, J=2.26 Hz, 1H), 6.08 (dd, J=17.32, 10.54 Hz, 1H), 5.28 (dd, J=10.54, 1.00 Hz, 1H), 5.18 (dd, J=17.32, 1.25 Hz, 1H), 5.09-5.13 (m, 2H), 4.44 (dd, J=10.54, 3.26 Hz, 1H), 4.27 (dd, J=10.42, 6.40 Hz, 1H), 3.77 (dd, J=6.78, 3.51 Hz, 1H), 1.64-1.88 (m, 3H), 1.07 (dd, J=6.40, 4.89 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 (0.1% TFA in water)

Sources & evidence

ORD record
ord-64880e938318431b97ebf58e6840615d
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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