1,4-Dioxane → HCID 23651430, compound

HRID 2382993Notes

Reaction equation

HRID 2382993 reaction equation
CC(C)([O-])C.[Na+].[F:7][C:8]1[CH:9]=[C:10]2[C:16]3([CH2:21][CH2:20][N:19]([CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[CH2:18][CH2:17]3)[CH2:15][N:14]([C:28]([N:30]([CH3:32])[CH3:31])=[O:29])[C:11]2=[CH:12][CH:13]=1.I[C:34]1[CH:39]=[N:38][CH:37]=[CH:36][N:35]=1.O1CCOCC1>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].CC#N>[F:7][C:8]1[CH:9]=[C:10]2[C:16]3([CH2:21][CH2:20][N:19]([CH:22]4[CH2:27][CH2:26][N:25]([C:34]5[CH:39]=[N:38][CH:37]=[CH:36][N:35]=5)[CH2:24][CH2:23]4)[CH2:18][CH2:17]3)[CH2:15][N:14]([C:28]([N:30]([CH3:32])[CH3:31])=[O:29])[C:11]2=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 642841IodopyrazineHCID 23676156Sodium t-butoxideHCID 59433352HCID 59433352, compound

Product 1

HCID 23651430HCID 23651430, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Pd2(dba)3 (0.5 mol %, 5.175 mg), ligand 12-(dicyclohexylphosphino)-2′ (N,N-dimethylamino) biphenyl (7.86 mg, 20 mol %), and sodium tert-butoxide (13.45 mg, 0.14 mmol) were weighed in air and transferred into a microwave tube. 5-fluoro-N,N-dimethyl-1′-(piperidin-4-yl)spiro[indoline-3,4′-piperidine]-1-carboxamide 4ba (36.0 mg, 0.1 mmol) and 2-iodo pyrazine (20.5 mg, 0.1 μmol) and 1 mL of dioxane were added. The tube was purged with N2 and stirred at 80° C. for 16 hours. The reaction was diluted with methanol, filtered (Whatman 0.2 μm PTFE) and subjected to reverse-phase HPLC purification [2-50% CH3CN gradient over 13 min with 0.1% TFA (aq), 35 mL/min, 1.5 mL injected] to provide compound no. 52. 1H NMR (400 MHz, MeOD) 8.63 (d, J=2.6 Hz, 1H), 8.52 (s, 1H), 7.92 (d, J=3.0 Hz, 1H), 7.28-7.23 (m, 2H), 7.03-6.98 (m, 2H), 4.75-7.72 (m, 2H), 3.93 (s, 2H), 3.70-3.78 (m, 3H), 3.33-3.18 (m, 4H), 3.00 (s, 6H), 2.42-2.35 (m, 4H), 2.05-1.92 (m, 4H). LC/MS (10-99% CH3CN/0.05% TFA gradient over 5 min): m/z 421.1, retention time 2.03 minutes.

Workup

  1. customtransferred into a microwave tube
  2. customThe tube was purged with N2
  3. additionThe reaction was diluted with methanol
  4. filtrationfiltered (Whatman 0.2 μm PTFE)
  5. customsubjected to reverse-phase HPLC purification [2-50% CH3CN gradient over 13 min with 0.1% TFA (aq), 35 mL/min, 1.5 mL injected]
  6. customto provide compound no

Sources & evidence

ORD record
ord-b26ff5bacc2e40958002e8122e089132
Source dataset
uspto-grants-2012_09
Patent number
US08263605B2

Reaction notes

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