Sodium hydride → 2-chloro-benzaldehyde O-(4-amino-5-fluoropyrimidin-2-yl)oxime

HRID 1403182Notes

Reaction equation

HRID 1403182 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[CH:6]=[N:7][OH:8].[F:13][C:14]1[C:15]([NH2:24])=[N:16][C:17](S(C)(=O)=O)=[N:18][CH:19]=1>O1CCCC1>[NH2:24][C:15]1[C:14]([F:13])=[CH:19][N:18]=[C:17]([O:8][N:7]=[CH:6][C:5]2[CH:9]=[CH:10][CH:11]=[CH:12][C:4]=2[Cl:3])[N:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 96239o-ChlorobenzaldoximeHCID 58318934HCID 58318934, compound

Product 1

HCID 767594182-chloro-benzaldehyde O-(4-amino-5-fluoropyrimidin-2-yl)oximeYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 60% NaH (0.063 g, 1.57 mmol) in anhydrous tetrahydrofuran (THF; 5 mL) was added in portions a solution of 2-chlorobenzaldehyde oxime (0.254 g, 1.64 mmol in 1 mL of THF) at room temperature, and the resulting frothy mixture was stirred for 1 h. To the resulting tan mixture was added 5-fluoro-2-methanesulfonylpyrimidin-4-ylamine (0.25 g, 1.31 mmol), at which point the reaction mixture turned orange and most of the solids dissolved. Within minutes of the addition a new solid had precipitated, and the resulting orange mixture was stirred at room temperature for 16 h. The entire reaction mixture was adsorbed to Celite (2.5 g) and the adsorbed material was purified by flash chromatography (24 g SiO2; 0→100% EtOAc/hexanes) to give 2-chlorobenzaldehyde O-(4-amino-5-fluoropyrimidin-2-yl)oxime (0.173 g, 50%) as a white solid: mp 220-230° C. dec; 1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.05 (d, J=3.1 Hz, 1H), 7.92 (dd, J=7.8, 1.5 Hz, 1H), 7.54 (m, 5H); ESIMS m/z 267 ([M+H]+), 265 ([M−H]−).

Workup

  1. dissolutiondissolved
  2. additionWithin minutes of the addition a new solid
  3. customhad precipitated
  4. stirringthe resulting orange mixture was stirred at room temperature for 16 h
  5. customThe entire reaction mixture
  6. customthe adsorbed material was purified by flash chromatography (24 g SiO2; 0→100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a2478bed754242649987ce2a03790f1f
Source dataset
uspto-grants-2014_12
Patent number
US08912207B2

Reaction notes

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