Dimethylformamide → N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}methanesulfonamide

HRID 573668Notes

Reaction equation

HRID 573668 reaction equation
[Br:1][C:2]1[S:12][C:5]2[N:6]=[C:7]([CH3:11])[CH:8]=[C:9]([NH2:10])[C:4]=2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1.CC(C)([O-])C.[Na+].[CH3:27][S:28](Cl)(=[O:30])=[O:29].CN(C=O)C>C1COCC1.C(OCC)(=O)C.O>[Br:1][C:2]1[S:12][C:5]2=[N:6][C:7]([CH3:11])=[CH:8][C:9]([NH:10][S:28]([CH3:27])(=[O:30])=[O:29])=[C:4]2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 31297Methanesulfonyl chloride2×HCID 23676156Sodium t-butoxide2×HCID 683240582-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine

Product 1

HCID 68323754N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}methanesulfonamideYield 32.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine (Description 17) (277 mg, 0.793 mmol) in THF (2.5 mL) at RT, was added sodium tert-butoxide (220 mg, 2.289 mmol). The reaction mixture was stirred at RT for 15 min, followed by the addition of methane sulfonyl chloride (0.14 mL, 1.797 mmol). The reaction mixture was stirred at 1 h at RT, followed by the addition of DMF (2.5 mL), another portion of sodium tert-butoxide (203 mg, 2.112 mmol) and methane sulfonyl chloride (0.14 mL, 1.797 mmol). The reaction mixture was stirred for another 1 h at RT before the addition of water (20 mL) and ethyl acetate (20 mL). The aqueous layer was separated and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed with water (15 mL), dried (phase separating column) and concentrated to give a residue. Purification on silica (twice), eluting with a gradient of 0-75% ethyl acetate in cyclohexane afforded the title compound (109 mg) which was of sufficient purity for subsequent steps. In addition, some impure fractions were isolated and these were combined and further purified by MDAP (acidic conditions), to give an analytically pure sample of the title compound (9 mg). LCMS (A) m/z: 427/429 [M+1]+, Rt 1.33 min (acidic).

Workup

  1. stirringThe reaction mixture was stirred at 1 h at RT
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (3×25 mL)
  4. washThe combined organic extracts were washed with water (15 mL)
  5. customdried
  6. custom(phase separating column)
  7. concentrationconcentrated
  8. customto give a residue
  9. customPurification on silica (twice),
  10. washeluting with a gradient of 0-75% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-1f8c547bf6044e5e89c3eb9241e4529a
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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