Hexachloroethane → [1-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-cyclopentyl]-dimethyl-amine

HRID 2282609Notes

Reaction equation

ClC(Cl)(Cl)C(Cl)(Cl)Cl.[F:9][C:10]1[CH:11]=[CH:12][C:13]([NH:16][NH:17][C:18]([C:20]2([N:25]([CH3:27])[CH3:26])[CH2:24][CH2:23][CH2:22][CH2:21]2)=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]=[CH:12][C:13]2[N:14]([C:18]([C:20]3([N:25]([CH3:27])[CH3:26])[CH2:24][CH2:23][CH2:22][CH2:21]3)=[N:17][N:16]=2)[CH:15]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Hexachloroethane (503 mg, 2.12 mmol) was added portionwise over 5 minutes at RT to a stirred mixture of Intermediate 99b (282 mg, 1.06 mmol), triethylamine (590 μL, 4.24 mmol) and triphenylphosphine (555 mg, 2.12 mmol) in THF (11 mL). The reaction mixture was stirred at 50° C. for 2.5 h and then partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC using SCX-2 cartridge. The cartridge was washed with MeOH and the product was eluted with 2M NH3 in MeOH to give the title compound (207 mg, 79%). 1H NMR (400 MHz, CDCl3): 1.67-1.78 (4H, m), 2.10-2.22 (8H, m), 2.24-2.34 (2H, m), 7.15 (1H, ddd, J=10.0, 7.4, 2.3 Hz), 7.69 (1H, dd, J=10.0, 5.0 Hz), 8.65-8.68 (1H, m).

Workup

custompartitioned between EtOAc and water
extractionThe aqueous phase was extracted with EtOAc (×3)
washthe combined organic layers were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe resultant residue was purified by FCC
washThe cartridge was washed with MeOH
washthe product was eluted with 2M NH3 in MeOH

Sources & evidence

ORD record: ord-8f41902a0cc64b08bf0bf9099c4c45df
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139584B2

Reaction notes

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