Potassium Carbonate → N-tert-butyl-5-(5-((tert-butyldimethylsilyloxy)methyl)-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophene-2-sulfonamide

HRID 1484942Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)[C:5]([CH2:17][O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:4][N:3]=1.[C:26]([NH:30][S:31]([C:34]1[S:38][C:37](B(O)O)=[CH:36][CH:35]=1)(=[O:33])=[O:32])([CH3:29])([CH3:28])[CH3:27].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[C:26]([NH:30][S:31]([C:34]1[S:38][C:37]([C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:13]=[C:12]([CH:14]4[CH2:16][CH2:15]4)[NH:11][N:10]=3)[C:5]([CH2:17][O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:4][N:3]=2)=[CH:36][CH:35]=1)(=[O:32])=[O:33])([CH3:29])([CH3:27])[CH3:28]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 2-bromo-5-((tert-butyldimethylsilyloxy)methyl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (210 mg, 0.49 mmol, 1.0 equiv.), 5-(N-tert-butylsulfamoyl)thiophen-2-ylboronic acid (260.4 mg, 0.99 mmol, 2 equiv.), PdCl2(dppf)CH2Cl2 (120.0 mg, 0.15 mmol, 0.3 equiv.), K2CO3 (236.67 mg, 1.72 mmol, 3.5 equiv.) in dioxane (10 mL) and water (2 mL) was heated for 12 h at 90° C. under nitrogen atmosphere. The solvent was removed and the residue was purified by silica gel chromatography (PE/EtOAc=5:12:1 as eluant) to give N-tert-butyl-5-(5-((tert-butyldimethylsilyloxy)methyl)-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophene-2-sulfonamide (120.0 mg, 43.5%) as white solid. LC-MS (m/z)=563.1 [M+H]+;

Workup

customThe solvent was removed
customthe residue was purified by silica gel chromatography (PE/EtOAc=5:12:1 as eluant)

Sources & evidence

ORD record: ord-95ae154aad0c4fd5b09604969bd8752d
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422271B2

Reaction notes

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