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3,4-dihydro-2H-pyran → N-[4-[[3-(3,4-Dihydro-2H-pyran-2-yl)-2-pyridinyl]oxy]phenyl]-2-pyridinamine

HRID 473659
Notes
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Reaction equation

HRID 473659 reaction equation
Cl.Br[C:3]1[C:4]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)=[CH:12][CH:11]=2)=[N:5][CH:6]=[CH:7][CH:8]=1.C1(N(C)C2CCCCC2)CCCCC1.[O:37]1[CH:42]=[CH:41][CH2:40][CH2:39][CH2:38]1>[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.O1CCOCC1>[O:37]1[CH:38]=[CH:39][CH2:40][CH2:41][CH:42]1[C:3]1[C:4]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)=[CH:12][CH:11]=2)=[N:5][CH:6]=[CH:7][CH:8]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 24210N-Methyl dicyclohexylamineHCID 67425919N-(4-(3-Bromopyridin-2-yloxy)phenyl)pyridin-2-amine hydrochloride

Product 1

HCID 59374292N-[4-[[3-(3,4-Dihydro-2H-pyran-2-yl)-2-pyridinyl]oxy]phenyl]-2-pyridinamine

Reagents, catalysts & solvents 2

HCID 2734558
Bis(tri-tert-butylphosphine)palladium(0)
Catalyst
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

To a 25 mL microwave vial was added Bis(tri-tert-butylphosphine) palladium (0) (101 mg, 0.198 mmol) and N-(4-(3-bromopyridin-2-yloxy)phenyl)pyridin-2-amine hydrochloride (750 mg, 1.981 mmol) before evacuating and backfilling with nitrogen (2×). After addition of Dioxane (5.659 ml), N-cyclohexyl-N-methylcyclohexanamine (0.840 ml, 3.96 mmol), and 3,4-dihydro-2H-pyran (666 mg, 7.92 mmol) was added and the mixture was heated to 105° C. Following complete consumption of the starting material, the reaction mixture was cooled to room temperature and the volatiles were removed under reduced pressure. Following silica gel chromatography, the title compound was obtained as a racemic mixture. MS (ESI, pos. ion) m/z: 346.0. IC50 (uM) 0.064.

Workup

  1. custombefore evacuating
  2. additionwas added
  3. customconsumption of the starting material
  4. temperaturethe reaction mixture was cooled to room temperature
  5. customthe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-c3626ddc923647bab10de00cd13c2f77
Source dataset
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08637500B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes