Iodopyrazine → 1'-(1-(pyrazin-2-yl)piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2(1H)-one

HRID 641191Notes

Reaction equation

HRID 641191 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N)=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+].Cl.Cl.[NH:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH2:46][CH2:45][C:44]3([O:51][C:50](=[O:52])[NH:49][C:48]4[CH:53]=[CH:54][CH:55]=[CH:56][C:47]3=4)[CH2:43][CH2:42]2)[CH2:37][CH2:36]1.I[C:58]1[CH:63]=[N:62][CH:61]=[CH:60][N:59]=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.O1CCOCC1>[N:59]1[CH:60]=[CH:61][N:62]=[CH:63][C:58]=1[N:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH2:46][CH2:45][C:44]3([O:51][C:50](=[O:52])[NH:49][C:48]4[CH:53]=[CH:54][CH:55]=[CH:56][C:47]3=4)[CH2:43][CH2:42]2)[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 642841IodopyrazineHCID 206074992'-(Dicyclohexylphosphino)biphenyl-2-amineHCID 23676156Sodium t-butoxideHCID 685788481'-(piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4'piperidin]-2(1H)-one bis-hydrochloride

Product 1

HCID 250601731'-(1-(pyrazin-2-yl)piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2(1H)-one

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 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Pd2(dba)3-CHCl3 (5 mg, 0.5 mol %), 2′-(dicyclohexylphosphino)biphenyl-2-amine (8 mg, 2 mol %) and sodium tert-butoxide (13 mg, 0.14 mmol) were weighed in air and transferred into flask, followed by dioxane (750 μL), 1′-(piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4′piperidin]-2(1H)-one bis-hydrochloride (compound no. 49) (37 mg, 0.10 mmol) and iodopyrazine (viia) (20.6 mg, 0.10 mmol). The flask was flushed with nitrogen and stirred at 80° C. for 16 hours. The reaction mixture was diluted with methanol (500 μL), filtered (Whatman 0.45 μm PTFE) and subjected to reverse-phase HPLC purification (2-25% CH3CN gradient [w/0.1% TFA (aq)] over 10 minutes, 1.0 mL injected, 35 mL/min) to provide 1′-(1-(pyrazin-2-yl)piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4′-piperidin]-2(1H)-one (compound no. 74). LC/MS m/z 380.2 [M+H]+, retention time 1.35 min (RP-C18, 10-99% CH3CN/0.05% TFA).

Workup

  1. customtransferred into flask
  2. customThe flask was flushed with nitrogen
  3. additionThe reaction mixture was diluted with methanol (500 μL)
  4. filtrationfiltered (Whatman 0.45 μm PTFE)
  5. customsubjected to reverse-phase HPLC purification (2-25% CH3CN gradient [w/0.1% TFA (aq)] over 10 minutes, 1.0 mL injected, 35 mL/min)

Sources & evidence

ORD record
ord-d6bbe3c8333a4e9a90eb273ba14a97c2
Source dataset
uspto-grants-2010_04
Patent number
US07696201B2

Reaction notes

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