Water → 2-(3-(3-Phenylpyrazin-2-YL)azetidin-1-YL)quinoline

HRID 1850320Notes

Reaction equation

HRID 1850320 reaction equation
Cl[C:2]1[C:3]([CH:8]2[CH2:11][N:10]([C:12]3[CH:21]=[CH:20][C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[N:13]=3)[CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O1CCOCC1>[C:22]1([C:2]2[C:3]([CH:8]3[CH2:11][N:10]([C:12]4[CH:21]=[CH:20][C:19]5[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=5)[N:13]=4)[CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 585467412-(3-(3-Chloropyrazin-2-yl)azetidin-1-yl)quinoline

Product 1

HCID 585474112-(3-(3-Phenylpyrazin-2-YL)azetidin-1-YL)quinolineYield 88%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 2-(3-(3-chloropyrazin-2-yl)azetidin-1-yl)quinoline (0.085 g, 0.286 mmol), phenylboronic acid (0.070 g, 0.573 mmol, Aldrich), potassium phosphate (0.152 g, 0.716 mmol, Alfa Aesar), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (0.020 g, 0.029 mmol, Aldrich), water (0.400 mL) and dioxane (1.6 mL). The mixture was purged with Argon gas and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 30 min. LCMS showed the product. The mixture was diluted with EtOAc and washed with Na2CO3 and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude was purified by silica gel chromatography (12 g, 10%-100% EtOAc-Hexane). The product was obtained as a white solid (85 mg, 88%).

Workup

  1. customA glass microwave reaction vessel
  2. customThe mixture was purged with Argon gas
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with Na2CO3 and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude was purified by silica gel chromatography (12 g, 10%-100% EtOAc-Hexane)

Sources & evidence

ORD record
ord-ff1e5fd35da5498baf2d944c354db4c7
Source dataset
uspto-grants-2015_02
Patent number
US08957073B2

Reaction notes

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