Diisopropylethylamine → 2-(2-(4-((6-Chloro-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972633Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[Cl:18][C:19]1[N:24]=[CH:23][C:22]([S:25]([N:28]2[CH2:33][CH2:32][NH:31][CH:30]([C:34]#[C:35][CH3:36])[CH2:29]2)(=[O:27])=[O:26])=[CH:21][CH:20]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[Cl:18][C:19]1[N:24]=[CH:23][C:22]([S:25]([N:28]2[CH2:33][CH2:32][N:31]([C:2]3[N:3]=[CH:4][C:5]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:10])([F:11])[F:12])=[CH:6][N:7]=3)[CH:30]([C:34]#[C:35][CH3:36])[CH2:29]2)(=[O:27])=[O:26])=[CH:21][CH:20]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (490 mg, 1.747 mmol, Intermediate D), 1-((6-chloropyridin-3-yl)sulfonyl)-3-(prop-1-yn-1-yl)piperazine (325 mg, 1.08 mmol), Hünig's base (1.0 mL, 5.73 mmol) and dioxane (5.0 mL) was heated at 120° C. for 15 h. The temperature was increased to 130° C. and stirring was continued for 24 h. The dark mixture was allowed to cool to room temperature and was then purified by silica gel chromatography (80 g silica gel, 10-50% EtOAc in hexane) to give 2-(2-(4-((6-chloro-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol as a white foam (0.664 g).

Workup

temperatureThe temperature was increased to 130° C.
temperatureto cool to room temperature
customwas then purified by silica gel chromatography (80 g silica gel, 10-50% EtOAc in hexane)

Sources & evidence

ORD record: ord-916cc305e4c842868426547113a6107a
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431563B2

Reaction notes

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