Sodium Hydroxide → Uplarafenib

HRID 929351Notes

Reaction equation

HRID 929351 reaction equation
[CH2:1]([S:4]([N:7]([C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[C:16]([C:22]([C:24]2[CH:25]=[C:26]3[C:31](=[CH:32][CH:33]=2)[N:30]=[CH:29][C:28]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[N:27]3)=[O:23])[C:15]=1[F:40])S(CCC)(=O)=O)(=[O:6])=[O:5])[CH2:2][CH3:3].[OH-].[Na+]>CO>[F:40][C:15]1[C:16]([C:22]([C:24]2[CH:25]=[C:26]3[C:31](=[CH:32][CH:33]=2)[N:30]=[CH:29][C:28]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[N:27]3)=[O:23])=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=1[NH:7][S:4]([CH2:1][CH2:2][CH3:3])(=[O:5])=[O:6]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86677176N-(propylsulfonyl)-N-(2,4,5-trifluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide

Product 1

HCID 71506198UplarafenibYield 68.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of N-(propylsulfonyl)-N-(2,4,5-trifluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide (41 mg, 0.068 mmol, 1.0 eq.) in MeOH/THE (10 mL/10 mL) was added 1 N NaOH (0.15 mmol, 2.2 eq.). The resulting mixture was stirred at rt for 1 h, then concentrated. The resulting residue was purified by flash column chromatography (PE/EA=1/1, v/v) to afford N-(2,4,5-trifluoro-3-(3-morpholinoquinoxaline-6-carbonyl)phenyl)propane-1-sulfonamide (23 mg, 68.9%). LRMS (M+H+) m/z calculated 495.1, found 495.1. 1H NMR (CDCl3, 400 MHz) δ 8.67 (s, 1 H), 7.98-8.03 (m, 3 H), 7.66-7.73 (m, 1 H), 6.72 (s, 1 H), 3.78-3.88 (m, 8H), 3.12-3.16 (t, 2 H), 1.87-1.92 (q, 2 H), 1.05-1.09 (t, 3 H).

Workup

  1. concentrationconcentrated
  2. customThe resulting residue was purified by flash column chromatography (PE/EA=1/1

Sources & evidence

ORD record
ord-0029c7a0d64d4c31872abb577d68dd1d
Source dataset
uspto-grants-2016_03
Patent number
US09295671B2

Reaction notes

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