Methanol → 6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-indazole-3-carboximidamide

HRID 2203336Notes

Reaction equation

C[Al](C)C.[Cl-].[NH4+:6].[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([C:26]#[N:27])=[N:13][N:14]2[CH2:17][CH2:18][C:19]([F:25])([F:24])[C:20]([F:23])([F:22])[F:21])=[CH:10][CH:9]=1.CO>C1(C)C=CC=CC=1>[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([C:26](=[NH:6])[NH2:27])=[N:13][N:14]2[CH2:17][CH2:18][C:19]([F:25])([F:24])[C:20]([F:21])([F:23])[F:22])=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Trimethylaluminum (2.0M in toluene, 23.17 mL, 46.3 mmol) was added dropwise to a suspension of ammonium chloride (2.49 g, 46.5 mmol) in 69 mL toluene cooled to 0° C. The solution was then stirred at room temperature for 3 hours. This solution was then added to the intermediate from Step D (3.0 g, 9.27 mmol) and then heated at 110° C. for 6 hours. The solution was then cooled to room temperature and carefully poured to silica gel (ca 150 mL) and methanol (ca 250 mL). After stirring for 1.5 hours the suspension was filtered and the filtrate concentrated to give the indicated product which was used in the next step without further purification. 1H NMR (400 MHz, CH3 CN-d3): selected peaks δ 8.26 (d, J=8.7 Hz, 1H); 7.70 (d, J=1.7 Hz, 1H); 7.24 (dd, J=8.7, 1.8 Hz, 1H); 4.67 (t, J=7.1 Hz, 2H); 3.01-2.78 (m, 2H). m/z=341.1 (M+H).

Workup

temperatureheated at 110° C. for 6 hours
temperatureThe solution was then cooled to room temperature
stirringAfter stirring for 1.5 hours the suspension
filtrationwas filtered
concentrationthe filtrate concentrated
customto give the indicated product which
customwas used in the next step without further purification

Sources & evidence

ORD record: ord-9bc9e40a70744e8ab280d24edf3bc4e2
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365574B2

Reaction notes

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