Triethylamine → HCID 67023851, compound

HRID 1038386Notes

Reaction equation

HRID 1038386 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[NH:14][C:13]([CH3:20])=[C:12]3[C:21]#[N:22])[CH:9]=2)[N:4]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[N:3]=1.[F:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][S:38](Cl)(=[O:40])=[O:39])=[CH:33][CH:32]=1.C(N(CC)CC)C>ClCCl>[C:21]([C:12]1[CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[N:3]=[C:2]3[NH:1][S:38]([CH2:37][C:34]2[CH:35]=[CH:36][C:31]([F:30])=[CH:32][CH:33]=2)(=[O:39])=[O:40])[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[NH:14][C:13]=1[CH3:20])#[N:22]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 2759108(4-fluorophenyl)methanesulfonyl Chloride2×HCID 24959832tert-Butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate

Product 1

HCID 67023851HCID 67023851, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 100 mg (0.256 mmol) tert-butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate (Example 3A) in dichloromethane (4 ml) were added 160 mg (0.77 mmol) (4-fluorophenyl)methanesulfonyl chloride and 0.11 ml (0.77 mmol) triethylamine. The mixture was stirred at reflux for 12 h. Then, further batches of 160 mg (0.77 mmol) (4-fluorophenyl)-methanesulfonyl chloride and 0.11 ml (0.77 mmol) triethylamine were added, and the mixture was again stirred at reflux for 1 h. After concentration under reduced pressure, the residue was dissolved in ethyl acetate and washed with brine. The aqueous layer was re-extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (acetonitrile/water gradient) to give 28 mg (19% of th.) of the title compound.

Workup

  1. temperatureat reflux for 12 h
  2. stirringthe mixture was again stirred
  3. temperatureat reflux for 1 h
  4. concentrationAfter concentration under reduced pressure
  5. dissolutionthe residue was dissolved in ethyl acetate
  6. washwashed with brine
  7. extractionThe aqueous layer was re-extracted with ethyl acetate
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by preparative RP-HPLC (acetonitrile/water gradient)

Sources & evidence

ORD record
ord-4741a947ac794c728f73f4f6c3c1b9b8
Source dataset
uspto-grants-2013_10
Patent number
US08551989B2

Reaction notes

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