Hydrochloric Acid → HCID 71251339, compound

HRID 1055052Notes

Reaction equation

[F:1][C:2]1[C:3]([NH:28][C@H:29]([C:37]([CH3:40])([CH3:39])[CH3:38])/[CH:30]=[CH:31]/[C:32]([O:34]CC)=[O:33])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)=[N:6][CH:7]=1.[Li+].[OH-].Cl>O1CCOCC1>[F:1][C:2]1[C:3]([NH:28][C@@H:29]([C:37]([CH3:40])([CH3:39])[CH3:38])/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][CH:9]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of (S,E)-ethyl 4-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-5,5-dimethylhex-2-enoate, 42a, (0.064 g, 0.112 mmol) in dioxane (2 mL) was added LiOH (2 mL of 2N solution). After heating at 100° C. for 2 hours, the mixture was acidified to pH 6 with 2N HCl. The aqueous phase was extracted with ethyl acetate (3×), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified via preparatory HPLC (CH3CN/H2O—TFA modifier) to afford 35 mg of the desired product as a TFA-salt: 1H NMR (300 MHz, MeOD) δ 8.54 (s, 1H), 8.50-8.18 (m, 3H), 7.18 (dd, J=15.7, 7.1 Hz, 1H), 6.08 (dd, J=15.7, 1.3 Hz, 1H), 5.21 (t, J=22.5 Hz, 1H), 1.12 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, (M+H) 388.23.

Workup

extractionThe aqueous phase was extracted with ethyl acetate (3×)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe resulting residue was purified via preparatory HPLC (CH3CN/H2O—TFA modifier)

Sources & evidence

ORD record: ord-845aa5fa6e1240348f0757a5c2e9aa54
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394302B2

Reaction notes

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