Tetrahydrofuran → 2-Cyclohexyl-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine

HRID 1360826Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:15])[S:13][CH:14]=2)=[CH:4][N:3]=1.[Br-].[CH:17]1([Zn+])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C1COCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:17]1([C:2]2[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]3[N:11]=[C:12]([CH3:15])[S:13][CH:14]=3)=[CH:4][N:3]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

Conditions

Temperature: 150 °C

Procedure

200 mg (0.85 mmol, 1 eq). 2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine, 50 mg (0.043 mmol, 0.05 eq) tetrakis(triphenylphosphine)palladium(0), and 2 mL of 0.5 M cyclohexylzinc bromide in THF (1 mmol, 1.1 eq) were combined. The reaction mixture was heated at 150° C. in the microwave for 5 min, quenched with pH 7 PBS, extracted with DCM. Silica gel chromatography (gradient 0% to 40% EtOAc/Hexanes) gave 2-cyclohexyl-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (L-001106449). The mono HCl salt was made by dissolving the free base into diethyl ether, adding 1 eq of HCl, and isolated by filtration. LC-MS calculated for C17H18N2S 282, observed m/e 283.3 (M+H)+. 1H-NMR (500 MHz, DMSO-d6) δ 8.87 (s, 1H), 8.30 (d, 1H), 8.03 (s, 1H), 7.71 (d, 1H), 2.94 (s, 1H), 2.69 (s, 3H), 1.35-1.91 (m, 10H).

Workup

customquenched with pH 7 PBS
extractionextracted with DCM

Sources & evidence

ORD record: ord-0c71a450d03d4d4fb13627c3b4821b35
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879882B2

Reaction notes

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