Water → HCID 10433901, compound

HRID 1376135Notes

Reaction equation

HRID 1376135 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]([CH3:38])=[CH:34][CH:33]=1)(=[O:31])=[O:30].O>C1COCC1>[CH3:27][N:28]([CH2:39][O:19][C:18]([C:10]1[NH:11][C:12]2[C:17]([C:9]=1[NH:8][C:5]1[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=1)=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:20])[S:29]([C:32]1[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=1)(=[O:30])=[O:31]

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 10433901HCID 10433901, compoundYield 23.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

Under N2 at 60° C. dissolve 3-(4-pyridinylamino)-1H-indole-2-carboxylic acid potassium salt (2.0 g, 6.89mmol) in a mixture of anhydrous THF and DMF (60:10 mL Cool to −5° C. add piperidinomethyl polystyrene HL resin (NOVA #01-64-0212, 30 mg) and follow with a solution of N-chloromethyl-N-methyl-4-methylbenzenesulfonamide (1.9 g, 8.34 mmol) in anhydrous THF (10 mL) dropwise. After 30 min, add water (100 mL) and then extract with dichloromethane (3×50 mL). Combine organic layers, wash with NaHCO3 (sat), water, brine, dry with MgSO4 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 a solid (1.1 g). Wash the solid with methanol/ether, and dry to give the title compound as a white solid (720 mg): TLC (silica gel, EtOAc/MeOH, 8:2), Rf=0.49, 1H NMR (DMSO-d6) δ 11.47 (1H, s), 8.32 (1H, s), 8.09 (2H, d, J=5.7 Hz), 7.63 (2H, d, J=8.3 Hz), 7.48 (1H, d, J=8.3 Hz), 7.34 (2H, m), 7.14 (3H, m), 6.52 (2H, d, J=6.0 Hz), 5.61 (2H, s), 2.83 (3H, s), 2.05 (3H, s).

Workup

  1. extractionextract with dichloromethane (3×50 mL)
  2. washCombine organic layers, wash with NaHCO3 (sat), water, brine
  3. dry with materialdry with MgSO4
  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 a solid (1.1 g)
  9. washWash the solid with methanol/ether
  10. customdry

Sources & evidence

ORD record
ord-72c10c2f2dec4455a9c1b7fe96f4fbe5
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

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