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HuagongsheHuagongshe Chemistry Print Report · For research reference only
HRID 60680Generated: October 29, 2026

Tetrahydrofuran → 1-[3-tert-Butyl-1'-(2-dimethylamino-ethyl)-3'-hydroxymethyl-1'H-[1,4']bipyrazolyl-5-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt

https://huagongshe.com/reaction/60680

Reaction equation

Participants

RoleNameHCIDCharge
ReactantTetrahydrofuranHCID 8028—
ReactantTetrabutylammonium FluorideHCID 2724141—
Reactant1-[3-tert-Butyl-1'-(2-dimethylamino-ethyl)-3'-triisopropylsilanyloxymethyl-1'H-[1,4']bipyrazolyl-5-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaHCID 123177122—
Product1-[3-tert-Butyl-1'-(2-dimethylamino-ethyl)-3'-hydroxymethyl-1'H-[1,4']bipyrazolyl-5-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate saltHCID 8634294632%

Reaction Conditions

Temperature50 °C

Reaction Steps

A solution of Intermediate 74k (76 mg, 0.088 mmol) in THF (0.44 mL) was treated with tetrabutylammonium fluoride (1M in THF, 0.44 mL, 0.44 mmol) and the mixture was heated to 50° C. for 5 h. The mixture was evaporated in vacuo and the residue was partitioned between DCM and a saturated aqueous sodium bicarbonate solution. The layers were separated and the aqueous layer was then extracted with DCM (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-9% [2M NH3 in MeOH] in DCM. Further purification by HPLC in 3 portions (Method 6, 30-60% MeCN in H2O, 0.1% HCO2H over 25 min) gave a colourless glass that was triturated with ether. The solid was collected by filtration, washed with ether and dried at 50° C. in vacuo to give the title compound (20 mg, 32%). LCMS (Method 5): Rt 3.47 min, m/z 710.5 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.3 Hz), 1.25 (9H, s), 1.44-1.57 (2H, m), 1.61-1.74 (2H, m), 1.74-1.92 (3H, m), 1.92-2.02 (1H, m), 2.01-2.16 (2H, m), 2.18 (6H, s), 2.68 (2H, t, J=6.8 Hz), 2.87-2.95 (1H, m), 3.16 (1H, dt, J=12.0, 4.1 Hz, partially obscured by water), 3.27-3.36 (11, m, obscured by water), 4.16 (2H, t, J=7.0 Hz), 4.31 (2H, s), 4.80-4.88 (1H, m), 4.92-5.11 (0.3H, br s), 5.53 (1H, t, J=4.3 Hz), 6.30 (1H, s), 7.14-7.22 (2H, m), 7.25-7.40 (41H, m), 7.64 (1H, d, J=10.0 Hz), 7.70 (1H, d, J=1.6 Hz), 8.00 (1H, s), 8.07 (1H, s), 8.19 (1H, s).

Provenance & Evidence

DOI10.6084/m9.figshare.5104873.v1
Patent numberUS09440974B2
Source datasetuspto-grants-2016_09
ORD IDord-1dbce7366e3b4b878839174710d2e9eb
Source noteuspto-grants-2016_09