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

HRID 573666Notes

Reaction equation

HRID 573666 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+].[CH:27]1([S:30](Cl)(=[O:32])=[O:31])[CH2:29][CH2:28]1.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:30]([CH:27]3[CH2:29][CH2:28]3)(=[O:32])=[O:31])=[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 2760919Cyclopropanesulfonyl chloride2×HCID 23676156Sodium t-butoxide2×HCID 683240582-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine

Product 1

HCID 68324162N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}cyclopropanesulfonamideYield 32.3%

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) (303 mg, 0.868 mmol) in THF (5 mL) at RT, was added sodium tert-butoxide (214 mg, 2.227 mmol). The reaction mixture was stirred at RT for 15 min, followed by the addition of cyclopropanesulfonyl chloride (0.16 mL, 1.74 mmol). The reaction mixture was stirred at RT for 1.5 h, followed by the sequential of addition of DMF (2.5 mL), sodium tert-butoxide (202 mg) and cyclopropanesulfonyl chloride (0.16 mL, 1.741 mmol). The reaction mixture was stirred at RT for another 1.5 h, followed by the addition of water (25 mL) and ethyl acetate (25 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, which was purified on silica, eluting with a gradient of 0-75% ethyl acetate in cyclohexane, to give a residue (127 mg). Ca. 45 mg of this material was purified further by MDAP (acidic conditions) followed by trituration with diethyl ether, to give the title compound (9 mg). LCMS (A) m/z: 453/455 [M+1]+, Rt 1.50 min (acidic).

Workup

  1. stirringThe reaction mixture was stirred at RT for 1.5 h
  2. stirringThe reaction mixture was stirred at RT for another 1.5 h
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (3×25 mL)
  5. washThe combined organic extracts were washed with water (15 mL)
  6. customdried
  7. custom(phase separating column)
  8. concentrationconcentrated
  9. customto give a residue, which
  10. customwas purified on silica
  11. washeluting with a gradient of 0-75% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-27463b3b5b6642158ef206da8f4a6a49
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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