Potassium Carbonate → N-[6-Methyl-3-[3-(methyloxy)phenyl]-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]cyclopropanesulfonamide

HRID 573667Notes

Reaction equation

Br[C:2]1[S:18][C:5]2=[N:6][C:7]([CH3:17])=[CH:8][C:9]([NH:10][S:11]([CH:14]3[CH2:16][CH2:15]3)(=[O:13])=[O:12])=[C:4]2[C:3]=1[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=1.C([O-])([O-])=O.[K+].[K+].[NH:33]1[CH:37]=[C:36](B(O)O)[CH:35]=[N:34]1>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:17][C:7]1[N:6]=[C:5]2[S:18][C:2]([C:36]3[CH:37]=[N:33][NH:34][CH:35]=3)=[C:3]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=3)[C:4]2=[C:9]([NH:10][S:11]([CH:14]2[CH2:16][CH2:15]2)(=[O:13])=[O:12])[CH:8]=1

Participants

Conditions

Temperature: 130 °C

Procedure

To a suspension of N-{2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}cyclopropanesulfonamide (Example 95) (58 mg, 0.128 mmol), K2CO3 (57 mg, 0.412 mmol) and 1H-pyrazol-4-ylboronic acid (30 mg, 0.268 mmol) in 1,4-dioxane (1 mL) and water (0.4 mL), was added tetrakis(triphenylphosphine)palladium(0) (15 mg, 0.013 mmol). The reaction mixture was heated at 130° C. in a microwave reactor for 1 h and was then directly loaded onto a silica column, eluting with a gradient of 0-75% of ethyl acetate in cyclohexane and further purified by MDAP (acidic then basic conditions) to give the desired product and a white solid thought to be a salt of the desired product. The solid material was subsequently dissolved in DCM (1 mL) and treated with acetic acid (ca. 0.5 mL). The solvent was then removed to give a residue which was combined with the initially obtained product and the mixture further purified on silica, eluting with a gradient of 0-75% ethyl acetate in cyclohexane, to give the title compound (18 mg). LCMS (A) m/z: 441 [M+1]+, Rt 1.08 min (acidic).

Workup

washeluting with a gradient of 0-75% of ethyl acetate in cyclohexane
customfurther purified by MDAP (acidic then basic conditions)

Sources & evidence

ORD record: ord-21fb80dd564b42e1981cb850ce79033a
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029545B2

Reaction notes

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