Potassium Carbonate → HCID 58169141, compound

HRID 1484933Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[S:10][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:12][CH:13]=2)O1.Br[C:20]1[N:25]=[C:24]([NH:26][C:27]2[CH:31]=[C:30]([CH:32]3[CH2:34][CH2:33]3)[NH:29][N:28]=2)[C:23]([C:35]#[C:36][Si](C)(C)C)=[CH:22][N:21]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>O>[CH:32]1([C:30]2[NH:29][N:28]=[C:27]([NH:26][C:24]3[C:23]([C:35]#[CH:36])=[CH:22][N:21]=[C:20]([C:9]4[S:10][C:11]([S:14]([CH3:17])(=[O:15])=[O:16])=[CH:12][CH:13]=4)[N:25]=3)[CH:31]=2)[CH2:34][CH2:33]1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4,4,5,5-tetramethyl-2-(5-(methylsulfonyl)thiophen-2-yl)-1,3,2-dioxaborolane (550 mg, 1.92 mmol, 1.5 eq), 2-bromo-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-((trimethylsilyl)ethynyl)pyrimidin-4-amine (480 mg, 1.28 mmol, 1.0 eq), PdCl2(dppf)CH2Cl2 (106.1 mg, 0.13 mmol, 0.1 eq), K2CO3 (529.0 mg, 3.84 mmol, 3.0 equiv.), dioxane (20 mL) and water (2 mL) was heated for 1 h at 90° C. under nitrogen atmosphere. The solvent was removed and the residue was purified by silica gel chromatography (PE/EtOAc=4:12:1 as eluant) to yield N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-ethynyl-2-(5-(methyl sulfonyl) thiophen-2-yl)pyrimidin-4-amine (Compound 255) (246 mg, 50%). LC-MS (m/z)=386 [M+H]+; 1H NMR (400 MHz, DMSO-d6): 0.73-0.77 (m, 2H), 0.96-1.01 (m, 2H), 1.93-1.99 (m, 1H), 3.41 (s, 3H), 4.91 (s, 1H), 6.42 (s, 1H), 7.87 (dd, J1=4.0 Hz, J2=7.2 Hz, 2H), 8.54 (s, 1H), 8.94 (s, 1H).

Workup

customThe solvent was removed
customthe residue was purified by silica gel chromatography (PE/EtOAc=4:12:1 as eluant)

Sources & evidence

ORD record: ord-66f4ee839f44409989be585bf02fc065
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422271B2

Reaction notes

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