Water → HCID 10026032, compound

HRID 1376134Notes

Reaction equation

HRID 1376134 reaction equation
[K+].[N:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[C:18]([O-:20])=[O:19])=[CH:4][CH:3]=1.CN(C=O)C.Cl[CH2:27][N:28]([CH3:39])[S:29]([C:32]1[CH:37]=[CH:36][C:35](C)=[CH:34][CH:33]=1)(=[O:31])=[O:30].O>C1COCC1>[C:32]1([S:29]([N:28]([CH2:39][O:19][C:18]([C:10]2[NH:11][C:12]3[C:17]([C:9]=2[NH:8][C:5]2[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)=[O:20])[CH3:27])(=[O:31])=[O:30])[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 12713982N-chloromethyl-N-methyl-4-methylbenzenesulfonamideHCID 690066653-(4-Pyridinylamino)-1h-indole-2-carboxylic acid potassium salt

Product 1

HCID 10026032HCID 10026032, compoundYield 24.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Under N2 at 60° C. dissolve 3-(4-pyridinylamino)-1H-indole-2-carboxylic acid potassium salt (2.2 g, 7.55 mmol) in a mixture of anhydrous THF and DMF (150:40 mL). Cool to 0° C. and add N-chloromethyl-N-methyl-4-methylbenzenesulfonamide (2.0 g, 9.10 mmol) in anhydrous THF (10 mL) dropwise. After 20 min., add water (100 mL) and then extract with dichloromethane (3×100 mL). Combine the organic layers wash with NaHCO3 (sat), water, brine, dry with Na2SO4 and then concentrate. Purify the residue on an ISCO RediSep 35-gram silicagel cartridge, eluting with 50% heptane/ethyl acetate, ethyl acetate and then 10% methanol/ethyl acetate. Combine product containing fractions and concentrate to an oil. Dissolve the oil in methanol and add ether to obtain the title compound as a white solid (800 mg): MS: 437(M+H), 1H NMR (DMSO-d6) δ 11.52 (1H, s), 8.29 (1H, s), 8.04 (2H, d, J=5.5 Hz), 7.76 (2H, d, J=7.2 Hz), 7.43 (6H, m), 7.03 (1H, m), 6.46 (2H, d, J=6.0 Hz), 5.60 (2H, s), 2.79 (3H, s).

Workup

  1. extractionextract with dichloromethane (3×100 mL)
  2. washCombine the organic layers wash with NaHCO3 (sat), water, brine
  3. dry with materialdry with Na2SO4
  4. concentrationconcentrate
  5. customPurify the residue on an ISCO RediSep 35-gram silicagel cartridge
  6. washeluting with 50% heptane/ethyl acetate, ethyl acetate
  7. additionCombine product containing fractions
  8. concentrationconcentrate to an oil
  9. dissolutionDissolve the oil in methanol
  10. additionadd ether

Sources & evidence

ORD record
ord-0d1eb346e1ac4596b80bdd2fdb3bba41
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

Loading…