Sodium Hydroxide → HCID 59375650, compound

HRID 2193027Notes

Reaction equation

HRID 2193027 reaction equation
I[C:2]1[CH:23]=[CH:22][C:5]2[C:6]([NH:15][CH:16]([CH3:21])[C:17]([CH3:20])([CH3:19])[CH3:18])=[N:7][C:8]3[CH:9]=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.N1CCC[C@H]1C(O)=O.[OH-].[Na+].[Na+].[CH3:35][S:36]([O-:38])=[O:37]>[Cu]I.CS(C)=O>[CH3:35][S:36]([C:2]1[CH:23]=[CH:22][C:5]2[C:6]([NH:15][CH:16]([CH3:21])[C:17]([CH3:20])([CH3:19])[CH3:18])=[N:7][C:8]3[CH:9]=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1)(=[O:38])=[O:37]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 59375501HCID 59375501, compound

Product 1

HCID 59375650HCID 59375650, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

9-Iodo-6-[(1,2,2-trimethylpropyl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one (130 mg, 0.31 mmol), copper(I) iodide (5.9 mg, 0.031 mmol), L-proline (7.1 mg, 0.062 mmol), sodium hydroxide (2.5 mg, 0.062 mmol), and methanesulfinic acid sodium salt (41 mg, 0.40 mmol) were combined in a vial. DMSO (2.0 ml) was added, and the resulting suspension was purged with argon (subsurface bubbling) for 5 min. The reaction mixture was stirred at 95° C. for 24 h. The crude material was precipitated out of solution by adding 2 mL of MeOH, followed by 1.5 mL of water. The solids were collected by vacuum filtration, and purified by preparative reverse phase HPLC, eluting with an acetonitrile/water (with 0.05% TFA as a modifier) gradient, to afford 9-(methylsulfonyl)-6-[(1,2,2-trimethylpropyl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (500 MHz, DMSO-D6) δ 11.33 (br s, 1H), 10.45 (s, 1H), 8.74 (d, 1H), 8.01 (dd, 1H), 7.59 (br d, 1H), 7.36 (d, 1H), 6.36 (d, 1H), 4.71 (pentet, 1H), 3.25 (s, 3H), 1.17 (d, 3H), 0.93 (s, 9H). LRMS (ESI) calc'd for (C19H23N3O3S) [M+H]+, 374.1; found 374.1.

Workup

  1. customthe resulting suspension was purged with argon (subsurface bubbling) for 5 min
  2. customThe crude material was precipitated out of solution
  3. additionby adding 2 mL of MeOH
  4. filtrationThe solids were collected by vacuum filtration
  5. custompurified by preparative reverse phase HPLC
  6. washeluting with an acetonitrile/water (with 0.05% TFA as a modifier) gradient

Sources & evidence

ORD record
ord-d35a512423e1480db47052f4d6d82cb4
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

Loading…