Triethylamine → N-[2-amino-5-(2-thienyl)phenyl]-6-(2,7-diazaspiro[3.5]non-7-yl)nicotinamide

HRID 2360562Notes

Reaction equation

HRID 2360562 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([NH:10][C:11]2[CH:16]=[C:15]([C:17]3[S:18][CH:19]=[CH:20][CH:21]=3)[CH:14]=[CH:13][C:12]=2[NH:22]C(=O)OC(C)(C)C)=[O:9])=[CH:4][CH:3]=1.CCN(CC)CC.[CH2:37]1[C:40]2([CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH2:39][N:38]1C(OC(C)(C)C)=O>CS(C)=O>[NH2:22][C:12]1[CH:13]=[CH:14][C:15]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)=[CH:16][C:11]=1[NH:10][C:8](=[O:9])[C:5]1[CH:4]=[CH:3][C:2]([N:43]2[CH2:44][CH2:45][C:40]3([CH2:37][NH:38][CH2:39]3)[CH2:41][CH2:42]2)=[N:7][CH:6]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 23282935tert-Butyl 2,7-diazaspiro[3.5]nonane-2-carboxylateHCID 57717453tert-Butyl 2-(6-chloronicotinamido)-4-(thiophen-2-yl)phenylcarbamate

Product 1

HCID 52916957N-[2-amino-5-(2-thienyl)phenyl]-6-(2,7-diazaspiro[3.5]non-7-yl)nicotinamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

tert-Butyl [2-{[(6-chloropyridin-3-yl)carbonyl]amino}-4-(2-thienyl)phenyl]carbamate F (20 mg, 0.088 mmol) was dissolved in 1 mL of DMSO and treated with Et3N (0.010 mL) and tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate (20 mg, 0.047 mmol). The mixture was stirred at 90° C. for 18 h, partitioned between EtOAc and saturated NaHCO3, dried (MgSO4), filtered and concentrated), concentrated and the residue was purified by chromatography on SiO2 (EtOAc/CH2Cl2, 0% to 100%). The residue was dissolved in 1 mL of 1:1 TFA/CH2Cl2, stirred for 1 h and concentrated. Neutralization with EtOAc/sat'd NaHCO3 extraction and drying (MgSO4) gave desired product, N-[2-amino-5-(2-thienyl)phenyl]-6-(2,7-diazaspiro[3.5]non-7-yl)nicotinamide, which was confirmed by MS (ESI+): cal'd [M+H]+ 420.2, obs'd 420.1.

Workup

  1. custompartitioned between EtOAc and saturated NaHCO3
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated),
  5. concentrationconcentrated
  6. customthe residue was purified by chromatography on SiO2 (EtOAc/CH2Cl2, 0% to 100%)
  7. dissolutionThe residue was dissolved in 1 mL of 1:1 TFA/CH2Cl2
  8. stirringstirred for 1 h
  9. concentrationconcentrated
  10. extractionNeutralization with EtOAc/sat'd NaHCO3 extraction
  11. dry with materialdrying (MgSO4)

Sources & evidence

ORD record
ord-2b4414ca3392415db7bb99428f96e4c3
Source dataset
uspto-grants-2014_04
Patent number
US08686020B2

Reaction notes

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