Hydrochloric Acid → 1-(6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-((6-(3-(methylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinolin-3-yl)ethanone trihydrochloride

HRID 2271836Notes

Reaction equation

[C:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]3[CH2:25][CH2:24][CH:23]([N:26](C)[C:27](=O)OC(C)(C)C)[CH2:22]3)=[N:19][CH:20]=1)=[CH:11][C:10]([C:35]1[CH:40]=[C:39]([F:41])[C:38]([OH:42])=[C:37]([Cl:43])[CH:36]=1)=[CH:9][CH:8]=2)(=[O:3])[CH3:2].O.[ClH:45]>C1COCC1>[ClH:43].[ClH:45].[ClH:43].[Cl:43][C:37]1[CH:36]=[C:35]([C:10]2[CH:11]=[C:12]3[C:7](=[CH:8][CH:9]=2)[N:6]=[CH:5][C:4]([C:1](=[O:3])[CH3:2])=[C:13]3[NH:14][C:15]2[CH:20]=[N:19][C:18]([N:21]3[CH2:25][CH2:24][CH:23]([NH:26][CH3:27])[CH2:22]3)=[CH:17][CH:16]=2)[CH:40]=[C:39]([F:41])[C:38]=1[OH:42]

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of tert-butyl (1-(5-((3-acetyl-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-4-yl)amino)pyridin-2-yl)pyrrolidin-3-yl)(methyl)carbamate (85 mg, 0.14 mmol) in THF (5 mL) was added water (3 mL) and HCl (6 M in water, 2 mL, 12 mmol). The reaction mixture was heated at 65° C. for 3 h, cooled to room temperature and concentrated. The resultant residue was triturated with dichloromethane to give the desired product (55 mg, 64%) as an orange solid. 1H NMR (500 MHz, MeOD) δ 9.31 (s, 1H), 8.31-8.23 (m, 2H), 8.10-8.03 (m, 2H), 7.95 (dd, J=9.4, 2.4 Hz, 1H), 7.22 (dd, J=11.5, 2.3 Hz, 1H), 7.18-7.11 (m, 2H), 4.14-4.08 (m, 2H), 3.98-3.86 (m, 2H), 3.83-3.74 (m, 1H), 2.84 (s, 3H), 2.79 (s, 3H), 2.71-2.60 (m, 1H), 2.47-2.36 (m, 1H). ESI MS m/z 506 [C27H25ClFN50O2+H]+; HPLC 97.4% (AUC), tR=9.62 min.

Workup

temperaturecooled to room temperature
concentrationconcentrated
customThe resultant residue was triturated with dichloromethane

Sources & evidence

ORD record: ord-9a4d690e1ad64d3d8aa5384630cbd4ee
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120749B2

Reaction notes

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