Tetrahydrofuran → HCID 9980033, compound

HRID 1376119Notes

Reaction equation

HRID 1376119 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([NH:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)=[C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8]2)=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].O1CCCC1.Cl[CH2:35][C:36]([N:38]([CH2:41][CH3:42])[CH2:39][CH3:40])=[O:37]>CN(C)C=O>[CH2:14]([O:13][C:11]([C:7]1[N:8]([CH2:35][C:36](=[O:37])[N:38]([CH2:41][CH3:42])[CH2:39][CH3:40])[C:9]2[C:5]([C:6]=1[NH:16][C:17]1[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=1)=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=2)=[O:12])[CH3:15]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 16844Chloro-N,N-diethylacetamideHCID 10470984HCID 10470984, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 9980033HCID 9980033, compoundYield 14.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Under nitrogen, stir and cool to 0° C. a mixture of ethyl 6-chloro-3-(4-pyridinylamino)indole-2-carboxylate (0.50 g, 1.58 mmol) in dimethylformamide (5 mL). Add a 1M solution of potassium tert-butoxide in tetrahydrofuran (1.7 mL, 1.7 mmol) over a 2 min period, and stir for 10 min. Add 2-chlor-N,N-diethylacetamide (0.22 mL, 1.6 mmol) in one portion and stir at ambient temperature overnight. Quench the reaction into water (35 mL), and extract the aqueous mixture with ethyl acetate (2×20 mL). Combine the extracts, wash with water (25 mL), brine (25 mL) and dry over MgSO4. Concentrate under vacuum, and chromatograph the residue on a Redisep silica gel cartridge (10 g) eluting with 5% methanol/dichloromethane to 20% methanol/dichloromethane. Combine all homogenous fractions and concentrate to obtain a solid. Recrystallize the solid from ethyl acetate and obtain 0.1 g of the title compound as a white solid: MS 429(M+H), m.p. 212–214° C.

Workup

  1. stirringstir for 10 min
  2. customQuench
  3. customthe reaction into water (35 mL)
  4. extractionextract the aqueous mixture with ethyl acetate (2×20 mL)
  5. washCombine the extracts, wash with water (25 mL), brine (25 mL)
  6. dry with materialdry over MgSO4
  7. concentrationConcentrate under vacuum, and chromatograph the residue on a Redisep silica gel cartridge (10 g)
  8. washeluting with 5% methanol/dichloromethane to 20% methanol/dichloromethane
  9. concentrationCombine all homogenous fractions and concentrate
  10. customto obtain a solid
  11. customRecrystallize the solid from ethyl acetate

Sources & evidence

ORD record
ord-4d8fbf96e10147ae8a5ef4bffb45f855
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

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