Potassium Carbonate → (S)-tert-butyl(1-((5-cyano-3-fluoro-6-(quinolin-6-ylamino)pyridin-2-yl)amino)-4-methylpentan-2-yl)carbamate

HRID 1620106Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].Cl[C:8]1[C:15]([F:16])=[CH:14][C:11]([C:12]#[N:13])=[C:10]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[N:24]=[CH:23][CH:22]=[CH:21]3)[N:9]=1.[C:28]([O:32][C:33](=[O:42])[NH:34][C@@H:35]([CH2:38][CH:39]([CH3:41])[CH3:40])[CH2:36][NH2:37])([CH3:31])([CH3:30])[CH3:29]>O1CCOCC1>[C:28]([O:32][C:33](=[O:42])[NH:34][C@@H:35]([CH2:38][CH:39]([CH3:40])[CH3:41])[CH2:36][NH:37][C:8]1[C:15]([F:16])=[CH:14][C:11]([C:12]#[N:13])=[C:10]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[N:24]=[CH:23][CH:22]=[CH:21]3)[N:9]=1)([CH3:31])([CH3:30])[CH3:29]

Participants

Conditions

Temperature: 140 °C

Procedure

Potassium carbonate (139 mg) and 6-chloro-5-fluoro-2-(quinolin-6-ylamino)nicotinonitrile (60 mg) were added to a tube containing a 1,4-dioxane (2 ml) solution containing (S)-tert-butyl(1-amino-4-methylpentan-2-yl)carbamate (76 mg) and the tube was sealed, followed by stirring with heating at 140° C. for 13.5 hours. The reaction solution was adjusted to room temperature and an insoluble precipitate was removed. Subsequently, the solvent was distilled away under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1), and a white solid of (S)-tert-butyl(1-((5-cyano-3-fluoro-6-(quinolin-6-ylamino)pyridin-2-yl)amino)-4-methylpentan-2-yl)carbamate (50 mg) was thus obtained.

Workup

customthe tube was sealed
customwas adjusted to room temperature
customan insoluble precipitate was removed
distillationSubsequently, the solvent was distilled away under reduced pressure
customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record: ord-3a7306bdd2ef4159bd03980f463d8472
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772320B2

Reaction notes

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