Diisopropylethylamine → 1,1,1-Trifluoro-2-(2-(2-(1-propyn-1-yl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-pyrimidinyl)-2-propanol

HRID 1972629Notes

Reaction equation

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

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 3-(1-propyn-1-yl)-1-(2-thiophenylsulfonyl)piperazine (55 mg, 0.203 mmol), 2-(2-chloro-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (100 mg, 0.441 mmol, Intermediate E), Hünig's base (100 μL, 0.573 mmol), and dioxane (2 mL) was heated in an Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 140° C. for 1 h and then at 160° C. for 3 h. The resulting red mixture was purified via silica gel chromatography (10-50% EtOAc in hexanes) to give 1,1,1-trifluoro-2-(2-(2-(1-propyn-1-yl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-pyrimidinyl)-2-propanol (18 mg) as a mixture of 4 isomers.

Workup

customThe resulting red mixture was purified via silica gel chromatography (10-50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-91b5b64fda454a0a9a91aca9cf3b2522
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431563B2

Reaction notes

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