Triethylamine → 8-[5-({[2-Amino-5-(2-thienyl)phenyl]amino}carbonyl)pyridin-2-yl]-N-ethyl-1,8-diazaspiro[4.5]decane-1-carboxamide

HRID 1984777Notes

Reaction equation

HRID 1984777 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.[CH2:30]([NH:32][C:33]([N:35]1[C:39]2([CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[CH2:38][CH2:37][CH2:36]1)=[O:34])[CH3:31].CCN(CC)CC>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]([C:5]1[CH:4]=[CH:3][C:2]([N:42]2[CH2:41][CH2:40][C:39]3([N:35]([C:33]([NH:32][CH2:30][CH3:31])=[O:34])[CH2:36][CH2:37][CH2:38]3)[CH2:44][CH2:43]2)=[N:7][CH:6]=1)=[O:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 57717453tert-Butyl 2-(6-chloronicotinamido)-4-(thiophen-2-yl)phenylcarbamateHCID 57717467n-Ethyl-1,8-diazaspiro[4.5]decane-1-carboxamide

Product 1

HCID 247451178-[5-({[2-Amino-5-(2-thienyl)phenyl]amino}carbonyl)pyridin-2-yl]-N-ethyl-1,8-diazaspiro[4.5]decane-1-carboxamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of intermediate F (82 mg, 0.19 mmol), N-ethyl-1,8-diazaspiro[4.5]-decane-1-carboxamide (73 mg, 0.35 mmol), and NEt3 (43 μL, 0.31 mmol) in 5 mL of DMSO was stirred at 90° C. for 12 h. The reaction mixture was partitioned between EtOAc and saturated NaHCO3, the organic layer was dried (MgSO4), filtered and concentrated. The residue was stirred in 2 mL of TFA and 2 mL of CH2Cl2 for 1 h at room temperature and concentrated. Reverse-phase chromatography (10 to 100% MeCN/water with 0.05% TFA) followed by neutralization with EtOAc/saturated NaHCO3 extraction and drying with MgSO4 gave the title compound: MS (ESI+): cal'd [M+H]+ 505.2, obs'd 505.2.

Workup

  1. customThe reaction mixture was partitioned between EtOAc and saturated NaHCO3
  2. dry with materialthe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. concentrationconcentrated
  6. extractionReverse-phase chromatography (10 to 100% MeCN/water with 0.05% TFA) followed by neutralization with EtOAc/saturated NaHCO3 extraction
  7. dry with materialdrying with MgSO4

Sources & evidence

ORD record
ord-a68fd1780a1f4e818f367a7d8b246fa7
Source dataset
uspto-grants-2009_06
Patent number
US07544695B2

Reaction notes

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