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

HRID 1173165Notes

Reaction equation

HRID 1173165 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][C:9]=1[NH:19][C:20]([C:22]1[CH:23]=[N:24][C:25](Cl)=[CH:26][CH:27]=1)=[O:21])(C)(C)C.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>[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][C:9]=1[NH:19][C:20](=[O:21])[C:22]1[CH:27]=[CH:26][C:25]([N:43]2[CH2:44][CH2:45][C:40]3([CH2:37][NH:38][CH2:39]3)[CH2:41][CH2:42]2)=[N:24][CH:23]=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-bb776e9005d84d6a9e3bb0270804560b
Source dataset
uspto-grants-2010_11
Patent number
US07834026B2

Reaction notes

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