Sodium Carbonate → N-(2-Chloro-5-(6-(pyridin-4-yl)imidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)dimethylaminosulfonamide

HRID 1025391Notes

Reaction equation

HRID 1025391 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:12]=[C:13]([NH:18][S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[C:14]([Cl:17])=[N:15][CH:16]=3)=[CH:9][N:10]=2)[CH:7]=1.Cl[C:26]1[C:31](NS(N(C)C)(=O)=O)=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][N:27]=1.BrC1C=CC2N(C(I)=CN=2)C=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[Cl:17][C:14]1[C:13]([NH:18][S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])=[CH:12][C:11]([C:8]2[N:6]3[CH:7]=[C:2]([C:30]4[CH:29]=[CH:28][N:27]=[CH:26][CH:31]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)=[CH:16][N:15]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 220316326-Bromo-3-iodoimidazo(1,2-a)pyridineHCID 77231275N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)dimethylaminosulfonamideHCID 86663319N-(5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-chloropyridin-3-yl)dimethylaminosulfonamide

Product 1

HCID 46913524N-(2-Chloro-5-(6-(pyridin-4-yl)imidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)dimethylaminosulfonamide

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

N-(5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-chloropyridin-3-yl)dimethylaminosulfonamide. To a 5 mL microwave tube was added N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)dimethylaminosulfonamide (0.200 g, 0.553 mmol), 6-bromo-3-iodoimidazo[1,2-a]pyridine (0.214 g, 0.664 mmol), 1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(II) (0.020 g, 0.028 mmol), sodium carbonate (0.691 mL, 1.383 mmol), and dioxane (3 mL). The resulting mixture was sealed and underwent microwave heating at 110° C. for 15 min. The solvent was removed. The residue was partitioned between pH 7 buffer (1M TRIS-HCL) and DCM. The aqueous layer was extracted more with DCM (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, 12 g SiO2, hexanes:acetone=80%:20%, Flow=30 mL/min). The solvent was removed in vacuo to afford the desired product as brown solid (180 mg). MS (ESI pos. ion) m/z: 429.7. Calcd exact mass for C14H13BrClN5O2S: 428.9. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.94 (s, 6H) 7.36 (d, J=9.65 Hz, 1H) 7.63 (d, J=9.50 Hz, 1H) 7.79 (s, 1H) 8.09 (s, 1H) 8.34 (s, 1H) 8.42 (s, 1H).

Workup

  1. customThe resulting mixture was sealed
  2. customThe solvent was removed
  3. customThe residue was partitioned between pH 7 buffer (1M TRIS-HCL) and DCM
  4. extractionThe aqueous layer was extracted more with DCM (2×10 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified
  8. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-a96f4676641c4e579852edce1dfbbc25
Source dataset
uspto-grants-2014_05
Patent number
US08729074B2

Reaction notes

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