Water → 3-(Pyridin-4-ylamino)-1H-indole-2-carboxylic acid [phenyl-(toluene-4-sulfonyl)-amino]-methyl ester

HRID 1376133Notes

Reaction equation

HRID 1376133 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]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[S:29]([C:32]1[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=1)(=[O:31])=[O:30].O>C1COCC1>[C:39]1([N:28]([CH2:27][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])[S:29]([C:32]2[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=2)(=[O:31])=[O:30])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 69006665HCID 69006665, compoundHCID 69007007N-chloromethyl-N-phenyl-4-methylbenzenesulfonamide

Product 1

HCID 100066233-(Pyridin-4-ylamino)-1H-indole-2-carboxylic acid [phenyl-(toluene-4-sulfonyl)-amino]-methyl esterYield 10.1%

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, 7.5 mmol) in a mixture of anhydrous THF and DMF (90:10 mL). Cool to 0° C. and add a solution of N-chloromethyl-N-phenyl-4-methylbenzenesulfonamide (2.6 g, 8.80 mmol) in anhydrous THF (5 mL) dropwise. After 20 min add water (100 mL) and then extract with ethyl acetate (4×50 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 ethyl acetate and then 30% methanol/ethyl acetate. Combine product containing fractions and concentrate to a solid. Dissolve the solid in methanol and precipitate with ether to give the title compound as a yellow solid (390 mg): ESI/MS 313 (M+H, 1H NMR (CD3OD) δ 8.05 (2H, 2br d, J=6.5 Hz, J=6.8 Hz), 7.38 (14H, m), 6.61 (2H, br d, J=7.0 Hz), 5.93 (2H, s), 2.44 (3H, s).

Workup

  1. extractionextract with ethyl acetate (4×50 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 ethyl acetate
  7. additionCombine product containing fractions
  8. concentrationconcentrate to a solid
  9. dissolutionDissolve the solid in methanol

Sources & evidence

ORD record
ord-a23807500d534ce686634be02f17fddf
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

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