Hydrochloric Acid → (R)-4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxy-N-(piperidin-3-yl)pyrimidin-2-amine

HRID 1529425Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28]2)[N:19]=1.Cl>O1CCOCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]2)[N:19]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To solution of (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (130 mg, 0.243 mmol) in dioxane (2 mL) was added HCl in dioxane (4 M, 2 mL) and the mixture was heated at 90° C. for overnight. The reaction was quenched with aq.NaHCO3 and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was washed with 50% EtOAc in petroleum ether to give (R)-4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxy-N-(piperidin-3-yl)pyrimidin-2-amine (22 mg, 22%). MS (ESI, pos. ion) m/z: 436.1 (M+1); 1H-NMR (400 MHz DMSO-d6): δ ppm: 11.78 (brs, 1H) 8.66 (s, 1H), 8.25 (s, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.41-7.46 (m, 1H), 7.21-7.22 (m, 3H), 6.70 (s, 1H), 6.48 (s, 1H), 3.80-3.83 (brs, 4H), 2.89-2.99 (m, 1H), 2.33-2.41 (m, 2H), 1.98-1.99 (m, 2H), 1.43-1.50 (m, 2H), 1.12-1.24 (m, 2H).

Workup

customThe reaction was quenched with aq
extractionNaHCO3 and extracted with EtOAc
dry with materialThe organic layer was dried (Na2SO4)
filtrationfiltered
concentrationconcentrated
washThe residue was washed with 50% EtOAc in petroleum ether

Sources & evidence

ORD record: ord-e90774d126fa47fcb47e3575745769b3
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

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