Hydroxyamine hydrochloride → (NZ)-N-[(2-chloro-4-fluorophenyl)-(3-fluoro-4-pyrimidin-5-yl-2-pyridinyl)methylidene]hydroxylamine

HRID 871160Notes

Reaction equation

HRID 871160 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:11]1[C:16]([F:17])=[C:15]([C:18]2[CH:19]=[N:20][CH:21]=[N:22][CH:23]=2)[CH:14]=[CH:13][N:12]=1)=O.Cl.[NH2:25][OH:26]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[C:9](/[C:11]1[C:16]([F:17])=[C:15]([C:18]2[CH:19]=[N:20][CH:21]=[N:22][CH:23]=2)[CH:14]=[CH:13][N:12]=1)=[N:25]/[OH:26]

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 86730413(2-Chloro-4-fluorophenyl)(3-fluoro-4-(pyrimidin-5-yl)pyridin-2-yl)methanone

Product 1

HCID 136622537(NZ)-N-[(2-chloro-4-fluorophenyl)-(3-fluoro-4-pyrimidin-5-yl-2-pyridinyl)methylidene]hydroxylamineYield 88%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of (2-chloro-4-fluorophenyl)(3-fluoro-4-(pyrimidin-5-yl)pyridin-2-yl)methanone (0.030 g, 0.090 mmol) and hydroxylamine hydrochloride (0.043 g, 0.615 mmol) in pyridine (Volume: 0.452 ml) was refluxed for 3 hr, allowed to cool to room temperature, and then concentrated in vacuo. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed (required a few drops of MeOH). Purification of the crude material by silica gel chromatography using an ISCO machine (4 g column, 18 mL/min, 0-100% EtOAc in hexanes over 11 min, tr=0.4, 2 min) gave the title compound (29 mg, 0.079 mmol, 88% yield) as a yellow residue. ESI MS (M+H)+=347.0.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe crude material was dissolved in a minimal amount of CH2Cl2
  3. customto be chromatographed (required a few drops of MeOH)
  4. customPurification of the crude material by silica gel chromatography
  5. customan ISCO machine (4 g column, 18 mL/min, 0-100% EtOAc in hexanes over 11 min, tr=0.4, 2 min)

Sources & evidence

ORD record
ord-db3d987639d544c1b0e09de638dbd524
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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