Hexachloroethane → 6-Fluoro-8-methyl-3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 2282629Notes

Reaction equation

ClC(Cl)(Cl)C(Cl)(Cl)Cl.[F:9][C:10]1[CH:11]=[C:12]([CH3:26])[C:13]([NH:16][NH:17][C:18]([C@@H:20]2[CH2:24][CH2:23][CH2:22][N:21]2[CH3:25])=O)=[N:14][CH:15]=1.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[F:9][C:10]1[CH:11]=[C:12]([CH3:26])[C:13]2[N:14]([C:18]([C@@H:20]3[CH2:24][CH2:23][CH2:22][N:21]3[CH3:25])=[N:17][N:16]=2)[CH:15]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Hexachloroethane (141 mg, 0.587 mmol) was added portionwise at RT to a stirred mixture of Intermediate 105c (74 mg, 0.293 mmol), triethylamine (166 μL, 1.17 mmol) and triphenylphosphine (154 mg, 0.587 mmol) in THF (5 mL). The reaction mixture was stirred at 80° C. for 2 h, then cooled to RT and filtered. The filtrate was concentrated in vacuo and the resultant residue was purified by SCX cartridge. The cartridge was washed with 10% MeOH in DCM and the product eluted with 10% (2M NH3 in MeOH) in DCM. The product containing fractions were concentrated in vacuo and the resultant residue was purified by FCC on silica, using a gradient of 1-10% MeOH in DCM, to afford the title compound (59 mg, 86%) as a colourless oil. 1H NMR (400 MHz, CDCl3): 1.88-2.12 (3H, m), 2.15-2.53 (5H, m), 2.69 (3H, s), 3.28 (1H, t, J=7.8 Hz), 4.01-4.15 (1H, m), 6.97 (1H, d, J=8.4 Hz), 8.50 (1H, s).

Workup

temperaturecooled to RT
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo
customthe resultant residue was purified by SCX cartridge
washThe cartridge was washed with 10% MeOH in DCM
washthe product eluted with 10% (2M NH3 in MeOH) in DCM
additionThe product containing fractions
concentrationwere concentrated in vacuo
customthe resultant residue was purified by FCC on silica

Sources & evidence

ORD record: ord-643157fa9c3a4ec0beb109a4d5e37ff2
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139584B2

Reaction notes

Loading…