Chlorosuccinimide → 8-((2-amino-2,4-dimethylpentyl)oxy)-9-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398394Notes

Reaction equation

HRID 1398394 reaction equation
C(OC(=O)[NH:7][C:8]([CH3:32])([CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[C:23]3[C:18](=[C:19]([CH3:24])[N:20]=[CH:21][CH:22]=3)[C:17](=[O:25])[N:16]([CH3:26])[C:15]=2[CH:27]=1)(C)(C)C.C1C(=O)N([Cl:41])C(=O)C1>C(#N)C>[NH2:7][C:8]([CH3:32])([CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:9][O:10][C:11]1[C:12]([Cl:41])=[CH:13][C:14]2[C:23]3[C:18](=[C:19]([CH3:24])[N:20]=[CH:21][CH:22]=3)[C:17](=[O:25])[N:16]([CH3:26])[C:15]=2[CH:27]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 89957266Tert-butyl(1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-2,4-dimethylpentan-2-yl)carbamate

Product 1

HCID 732140208-((2-amino-2,4-dimethylpentyl)oxy)-9-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 13.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To the stirred solution of 8-((2-amino-2,4-dimethylpentyl)oxy)-4,6 dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (Prepared in Example 32, Part B) (0.08 g, 0.226 mmol) in acetonitrile (5 mL) was added NCS (0.030 g, 0.226 mmol)) at RT and the reaction mixture was stirred for 2 h. The mixture was then evaporated to dryness. The residue was purified by reverse phase HPLC (0.1% TFA in water/AcCN) to afford 8-((2-amino-2,4-dimethylpentyl)oxy)-9-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (12 mg, 0.030 mmol, 13% yield). LC/MS (ESI) m/e 388.0 [(M+H)+, calcd for C21H27ClN3O2, 388.2] as an off-white solid. LC/MS retention time (method C): tR=2.13 min. HPLC retention time (method A): tR=8.97 min; HPLC retention time (method B): tR=10.16 min. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.99-1.02 (m, 6H), 1.30 (s, 3H), 1.54-1.66 (m, 2H), 1.84-1.90 (m, 1H), 3.05 (s, 1H), 3.73 (s, 1H), 4.04 (q, J=23.20 Hz, 2H), 7.03 (s, 1H), 8.06 (d, J=6.00 Hz, 1H), 8.39 (s, 1H), 8.54 (d, J=6.00 Hz, 1H).

Workup

  1. customThe mixture was then evaporated to dryness
  2. customThe residue was purified by reverse phase HPLC (0.1% TFA in water/AcCN)

Sources & evidence

ORD record
ord-99323c73ed73492e9f9ae7e807da7b5a
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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