Triethylamine → 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-N-hydroxy-2-methyl-N'-pyridin-2-ylmethyl-benzamidine

HRID 471370Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([CH:18]=[N:19][OH:20])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.ClN1C(=O)CCC1=O.[N:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:42][NH2:43].C(N(CC)CC)C.[NH4+].[Cl-]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:25])([F:27])[F:26])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH:19][OH:20])=[N:43][CH2:42][C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][N:36]=4)=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzaldehyde-oxime ((i.e. the product of Example 1 Step 2, 177 mg, 0.42 mmol) in DMF (4 mL) was added N-chlorosuccinimide (67 mg, 0.50 mmol) and the mixture was stirred at 70° C. bath temperature for 30 min. After cooling to 0° C., picolylamine (85 mg, 0.79 mmol) and triethylamine (145 mg, 1.44 mmol) was added. The mixture was allowed to war to room temperature over night and was then poured on ice water. The pH was adjusted to 7 by addition of NH4Cl and the resulting precipitate was filtered off. The crude product was then purified by column chromatography on SiO2 (CH2Cl2: MeOH=96:4) to give the title compound (75 mg, 42%).

Workup

temperatureAfter cooling to 0° C.
waitThe mixture was allowed to war to room temperature over night
additionwas then poured on ice water
filtrationthe resulting precipitate was filtered off
customThe crude product was then purified by column chromatography on SiO2 (CH2Cl2: MeOH=96:4)

Sources & evidence

ORD record: ord-973c6622ab56469b991bcd590b10abed
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633134B2

Reaction notes

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