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 1802555Notes

Reaction equation

HRID 1802555 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.[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>[NH2:7][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:27]=[CH:26][C:25]([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:24][CH:23]=1)=[O:21]

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-f961e0c8bdac4207a731ec9f77180333
Source dataset
uspto-grants-2013_01
Patent number
US08349825B2

Reaction notes

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