Acetonitrile → HCID 70654684, compound

HRID 2091582Notes

Reaction equation

HRID 2091582 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[CH:9]1([NH:12][S:13]([C:16]2[CH:21]=[CH:20][C:19](B3OC(C)(C)C(C)(C)O3)=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:19]2[CH:20]=[CH:21][C:16]([S:13]([NH:12][CH:9]3[CH2:11][CH2:10]3)(=[O:15])=[O:14])=[CH:17][CH:18]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 706222-Amino-5-bromopyridineHCID 16414186N-Cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1-sulfonamide

Product 1

HCID 70654684HCID 70654684, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-amino-5-bromopyridine (3.58 g, 20.7 mmol), N-cyclopropyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzenesulfonamide (5.00 g, 20.7 mmol), sodium carbonate (3.29 g, 31.05 mmol), and PdCl2(PPh3)2 (0.436 g, 0.62 mmol) in 3:1 acetonitrile:water was microwave heated at 80° C. for 20 min, and then at 100° C. for 15 min. The reaction was then heated in an oil bath at 80° C. for 16 h. The reaction was cooled to room temperature and filtered. The solid was washed with methanol (10 mL), and the combined filtrates were concentrated. The crude material was purified by flash chromatography over silica gel (0-5% MeOH/DCM) to give 4-(6-aminopyridin-3-yl)-N-cyclopropylbenzenesulfonamide (2.08 g, 35% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.27 (d, J=2.01 Hz, 1H), 7.88-7.95 (m, 2H), 7.85 (d, J=2.51 Hz, 1H), 7.81-7.84 (m, 1H), 7.71-7.79 (m, 2H), 6.45-6.88 (m, 1H), 1.89-2.41 (m, 1H), 0.13-0.82 (m, 4H); MS (EI) m/z: 290 [M+H]+. HPLC (Sunfire C18 4.6 mm×50 mm, 10-90% MeCN:10 mM aq. NH4OAc, 2 min gradient) tR=1.34 min, 88% integrated area.

Workup

  1. temperatureThe reaction was then heated in an oil bath at 80° C. for 16 h
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered
  4. washThe solid was washed with methanol (10 mL)
  5. concentrationthe combined filtrates were concentrated
  6. customThe crude material was purified by flash chromatography over silica gel (0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-4ba8041b0fd645e9ab23fad0f9e1f8aa
Source dataset
uspto-grants-2013_05
Patent number
US08440652B2

Reaction notes

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