1-Methylpyrrolidine → 1-(4-Bromo-2-fluoro-5-(7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3,3-dimethylbutyl)urea

HRID 522735Notes

Reaction equation

[CH3:1][C:2]([CH3:7])([CH3:6])[CH2:3][CH2:4][NH2:5].[Br:8][C:9]1[C:14]([C:15]2[C:26]([CH3:27])=[N:25][C:18]3[N:19]=[C:20]([S:23][CH3:24])[N:21]=[CH:22][C:17]=3[CH:16]=2)=[CH:13][C:12]([NH:28][C:29](=O)[O:30]C(C)=C)=[C:11]([F:35])[CH:10]=1.CN1CCCC1>O1CCOCC1>[Br:8][C:9]1[C:14]([C:15]2[C:26]([CH3:27])=[N:25][C:18]3[N:19]=[C:20]([S:23][CH3:24])[N:21]=[CH:22][C:17]=3[CH:16]=2)=[CH:13][C:12]([NH:28][C:29]([NH:5][CH2:4][CH2:3][C:2]([CH3:7])([CH3:6])[CH3:1])=[O:30])=[C:11]([F:35])[CH:10]=1

Participants

Conditions

Temperature: 65 °C

Procedure

Treat a solution of 3,3-dimethylbutan-1-amine (0.080 g, 0.790 mmol) and prop-1-en-2-yl (4-bromo-2-fluoro-5-(7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl)phenyl)carbamate (0.244 g, 0.527 mmol) in dioxane (5 mL) with 1-methylpyrrolidine (4.48 mg, 0.053 mmol), heat at 65° C. for 3 h, then cool to RT overnight. Collect the resulting solid via filtration; concentrate the filtrate to dryness and purify via silica gel chromatography (10-30% EtOAc/DCM). Combine the two solids to afford the title compound (260 mg, 97% yield). MS (m/z): 506.1/508.1 (M+1).

Workup

temperaturecool to RT overnight
customCollect the resulting solid
filtrationvia filtration
concentrationconcentrate the filtrate to dryness
custompurify via silica gel chromatography (10-30% EtOAc/DCM)

Sources & evidence

ORD record: ord-099d38433c20484c99229214443a4c8c
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334267B2

Reaction notes

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