Nitrogen → HCID 73214161, compound

HRID 1398411Notes

Reaction equation

HRID 1398411 reaction equation
[CH:1]([O:4][CH2:5][C@H:6]([NH:25]C(=O)OCC1C=CC=CC=1)[CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:21]3[C:16](=[CH:17][N:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[N:14]([CH3:23])[C:13]=2[CH:24]=1)([CH3:3])[CH3:2].N#N>CO.[Pd]>[NH2:25][C@@H:6]([CH2:5][O:4][CH:1]([CH3:3])[CH3:2])[CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:21]3[C:16](=[CH:17][N:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[N:14]([CH3:23])[C:13]=2[CH:24]=1

Participants

5

Reactant 2

HCID 947NitrogenHCID 86710400HCID 86710400, compound

Product 1

HCID 73214161HCID 73214161, compoundYield 83.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of (S)-benzyl (1-isopropoxy-3-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)propan-2-yl)carbamate (220 mg, 0.130 mmol) in MeOH (12 mL) was degassed with N2 for 5 min. Pd/C (68.9 mg, 0.065 mmol) was added and the mixture stirred under a balloon of H2 for 12 h. The reaction mixture was filtered through diatomaceous earth (Celite®), eluting with methanol and the filtrate was concentrated under reduced pressure. The residue was purified by reverse phase HPLC (10 MM ammonium acetate in water/AcCN) to afford (S)-8-(2-amino-3-isopropoxypropoxy)-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (90 mg, 0.108 mmol, 83% yield) as an off-white solid. LC/MS (ESI) m/e 342.2, [(M+H)+, calcd for C19H24N3O3, 342.2]; LC/MS retention time (method C): tR=1.50 min. HPLC retention time (method A): tR=7.20 min; HPLC retention time (method B): tR=8.00 min. 1H NMR (400 MHz, MeOD) δ ppm 9.54 (s, 1H), 8.23 (d, J=4.4 Hz, 1H), 8.52 (d, J=8.8 Hz, 1H), 8.44 (d, J=6.0 Hz, 1H), 7.20 (s, 1H), 7.18 (d, J=6.0 Hz, 1H), 4.52 (dd, J=10.4, 3.6 Hz, 1H), 4.43 (dd, J=10.4, 6.8 Hz, 1H), 3.88-3.75 (m, 7H), 1.26 (d, J=6.4 Hz, 3H), 1.25 (d, J=6.4 Hz, 3H).

Workup

  1. filtrationThe reaction mixture was filtered through diatomaceous earth (Celite®)
  2. washeluting with methanol
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by reverse phase HPLC (10 MM ammonium acetate in water/AcCN)

Sources & evidence

ORD record
ord-e8e0645e30a5433a89f83b982b4715ad
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

Loading…