1,4-Dioxane → 1-(1-(5,6-dimethylpyrazin-2-yl)piperidin-4-yl)-N,N-dimethyl-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide

HRID 2382992Notes

Reaction equation

HRID 2382992 reaction equation
CC(C)([O-])C.[Na+].O1CCOCC1.[CH3:13][N:14]([CH3:38])[C:15]([N:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]2([CH2:31][CH2:30][N:29]([CH:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)[CH2:28][CH2:27]2)[CH2:19][CH2:18]1)=[O:16].Cl[C:40]1[N:41]=[C:42]([CH3:47])[C:43]([CH3:46])=[N:44][CH:45]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(Cl)(Cl)Cl.CC#N>[CH3:47][C:42]1[N:41]=[CH:40][C:45]([N:35]2[CH2:36][CH2:37][CH:32]([N:29]3[CH2:28][CH2:27][C:20]4([C:21]5[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=5)[N:17]([C:15]([N:14]([CH3:38])[CH3:13])=[O:16])[CH2:18][CH2:19]4)[CH2:31][CH2:30]3)[CH2:33][CH2:34]2)=[N:44][C:43]=1[CH3:46]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 126003905-Chloro-2,3-dimethylpyrazineHCID 23676156Sodium t-butoxideHCID 24798103N,N-dimethyl-1-(piperidin-4-yl)-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide

Product 1

HCID 236517101-(1-(5,6-dimethylpyrazin-2-yl)piperidin-4-yl)-N,N-dimethyl-2',3'-dihydrospiro[piperidine-4,4'-quinoline]-1'-carboxamide

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Pd2(dba)3-CHCl3 (5 mg, 0.5 mol %), ligand 1 (8 mg, 2 mol %) and 1.4 eq sodium tert-butoxide (13 mg, 0.14 mmol) were weighed in air and transferred into a microwave tube, followed by dioxane (750 μL), 1.0 eq N,N-dimethyl-1-(piperidin-4-yl)-2′H-spiro[piperidine-4,4′-quinoline]-1′(3′H)-carboxamide (36 mg, 0.10 mmol) and 1.0 eq 5-chloro-2,3-dimethylpyrazine (14 mg). The tube was flushed with nitrogen, capped and stirred at 80° C. for 3 hours. The reaction was cooled to room temperature, diluted with methanol (500 μL), filtered (Whatman 0.45 μm PTFE) and subjected to reverse-phase HPLC purification (2-40% CH3CN gradient [w/0.1% TFA (aq)] over t=10 minutes, 750 μL injected, 35 mL/min) to yield compound no. 20. LC/MS (10-99% CH3CN/0.05% TFA gradient over 5 min): m/z 463.4, retention time 2.13 minutes.

Workup

  1. customtransferred into a microwave tube
  2. customThe tube was flushed with nitrogen
  3. customcapped
  4. temperatureThe reaction was cooled to room temperature
  5. additiondiluted with methanol (500 μL)
  6. filtrationfiltered (Whatman 0.45 μm PTFE)
  7. customsubjected to reverse-phase HPLC purification (2-40% CH3CN gradient [w/0.1% TFA (aq)] over t=10 minutes, 750 μL injected, 35 mL/min)
  8. customto yield compound no

Sources & evidence

ORD record
ord-73f0c82dd4c8472d9903265ffd7f2dc5
Source dataset
uspto-grants-2012_09
Patent number
US08263605B2

Reaction notes

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