Ethyl Acetate → 3-Chloro-N-(3-{3-[(dimethylamino)methyl]phenyl}-2,6-dimethylthieno[2,3-b]pyridin-4-yl)benzenesulfonamide

HRID 573644Notes

Reaction equation

HRID 573644 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:22])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[CH3:23].Cl.[CH3:25][N:26]([CH3:43])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>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>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[C:7]([CH3:22])[N:6]=[C:5]3[S:4][C:3]([CH3:23])=[C:2]([C:30]4[CH:31]=[CH:32][CH:33]=[C:28]([CH2:27][N:26]([CH3:43])[CH3:25])[CH:29]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 44118822N,N-Dimethyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanamine hydrochlorideHCID 68324076N-(3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-yl)-3-chlorobenzenesulfonamide

Product 1

HCID 683240413-Chloro-N-(3-{3-[(dimethylamino)methyl]phenyl}-2,6-dimethylthieno[2,3-b]pyridin-4-yl)benzenesulfonamideYield 17%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Under nitrogen, N-(3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-yl)-3-chlorobenzene sulfonamide (Example 61) (80 mg, 0.185 mmol) was dissolved in 1,4-dioxane (1.5 mL) and water (0.5 mL). N,N-Dimethyl-1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanamine hydrochloride (83 mg, 0.278 mmol), tetrakis(triphenylphosphine)palladium(0) (21.41 mg, 0.019 mmol) and potassium carbonate (51.2 mg, 0.371 mmol) were added and heated in a microwave at 120° C. for 15 min. Ethyl acetate (10 mL) was added and washed with water (2×5 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo. The residue was purified by normal phase chromatography, eluting with a gradient of 0-20% 2M NH3 in MeOH in DCM, to give the title compound (15.3 mg). LCMS (A) m/z: 486 [M+1]+, Rt 0.92 min (acidic).

Workup

  1. washwashed with water (2×5 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customsolvent removed in vacuo
  5. customThe residue was purified by normal phase chromatography
  6. washeluting with a gradient of 0-20% 2M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-32b74ac28cc34f45bec993c922dc9cec
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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