Triethylamine → 6-Cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-(1-methyl-piperidin-4-ylsulfamoyl)-benzylamide

HRID 2382971Notes

Reaction equation

HRID 2382971 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:19]([OH:21])=O)[C:6]2[CH:7]=[N:8][N:9]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[C:10]=2[CH:11]=1)#[N:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH2:62][CH2:63][C:64]1[CH:69]=[CH:68][C:67]([S:70]([NH:73][CH:74]2[CH2:79][CH2:78][N:77]([CH3:80])[CH2:76][CH2:75]2)(=[O:72])=[O:71])=[CH:66][CH:65]=1>CN(C=O)C.O.C(OCC)(=O)C>[CH3:80][N:77]1[CH2:76][CH2:75][CH:74]([NH:73][S:70]([C:67]2[CH:68]=[CH:69][C:64]([CH2:63][NH:62][C:19]([C:5]3[C:6]4[CH:7]=[N:8][N:9]([C:12]5[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=5)[C:10]=4[CH:11]=[C:3]([C:1]#[N:2])[CH:4]=3)=[O:21])=[CH:65][CH:66]=2)(=[O:72])=[O:71])[CH2:79][CH2:78]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 433735484-(Aminomethyl)-N-(1-methylpiperidin-4-yl)benzenesulfonamideHCID 581389176-cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid

Product 1

HCID 581387966-Cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-(1-methyl-piperidin-4-ylsulfamoyl)-benzylamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 6-cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid (0.040 g, 0.14 mmol) in DMF (15 mL) was added PyBOP (0.1 g, 0.2 mmol) and triethylamine (0.04 g, 0.3 mmol) at room temperature. After 15 minutes, 4-aminomethyl-N-(1-methyl-piperidin-4-yl)-benzenesulfonamide (0.05 g, 0.16 mmol) was added. After 5 hours, the mixture was diluted with water (30 mL) and ethyl acetate (30 mL). The organic layer separated and washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography eluting with a gradient of 30-50% ethyl acetate in hexanes to afford the title compound.

Workup

  1. waitAfter 5 hours
  2. customThe organic layer separated
  3. washwashed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with a gradient of 30-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f968dc219e024c7d969edebff6838cb3
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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