Propargyl alcohol → (S)-(1-(2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutyl)-1H-1,2,3-triazol-4-yl)methanol

HRID 2171946Notes

Reaction equation

[CH2:1]([OH:4])[C:2]#[CH:3].[N:5]([CH2:8][C@@H:9]([NH:14][C:15]1[C:20]([F:21])=[CH:19][N:18]=[C:17]([Cl:22])[N:16]=1)[C:10]([CH3:13])([CH3:12])[CH3:11])=[N+:6]=[N-:7]>C1COCC1.C1(C)C=CC=CC=1>[Cl:22][C:17]1[N:16]=[C:15]([NH:14][C@@H:9]([C:10]([CH3:12])([CH3:11])[CH3:13])[CH2:8][N:5]2[CH:3]=[C:2]([CH2:1][OH:4])[N:7]=[N:6]2)[C:20]([F:21])=[CH:19][N:18]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of prop-2-yn-1-ol (0.22 g, 3.85 mmol) and (S)—N-(1-azido-3,3-dimethylbutan-2-yl)-2-chloro-5-fluoropyrimidin-4-amine, 216a, (0.21 g, 0.77 mmol) in THF (4 mL) and toluene (4 mL) was heated in a pressure vial at 120° C. for 8 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The crude product which contained two regioisomers was purified by silica gel chromatography (0-5% MeOH/CH2Cl2 gradient) to afford 100 mg of desired regioisomer, 217a, as well as 70 mg of the minor regioisomer (5-hydroxymethyl triazole).

Workup

temperatureThe reaction mixture was cooled to room temperature
concentrationconcentrated under reduced pressure
customwas purified by silica gel chromatography (0-5% MeOH/CH2Cl2 gradient)

Sources & evidence

ORD record: ord-27a388e6fff94e369cde3cec76e1f59b
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09051319B2

Reaction notes

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