Water → tert-Butyl 4-(5-(2-formyl-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)pyridin-2-yl)piperazine-1-carboxylate

HRID 1772629Notes

Reaction equation

HRID 1772629 reaction equation
Br[C:2]1[N:7]2[CH:8]=[C:9]([CH:11]=[O:12])[N:10]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[CH:29][C:30]([N:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)=[N:31][CH:32]=2)O1.C([O-])([O-])=O.[Na+].[Na+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:11]([C:9]1[N:10]=[C:6]2[C:5]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:4][CH:3]=[C:2]([C:27]3[CH:28]=[CH:29][C:30]([N:33]4[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]4)=[N:31][CH:32]=3)[N:7]2[CH:8]=1)=[O:12]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 16217947Tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylateHCID 1177281135-Bromo-8-morpholinoimidazo[1,2-a]pyrazine-2-carbaldehyde

Product 1

HCID 117733760tert-Butyl 4-(5-(2-formyl-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)pyridin-2-yl)piperazine-1-carboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of compound 2a (200 mg, 0.643 mmol) and tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylate (300 mg, 0.771 mmol) in 1,4-dioxane (10 mL) was added Na2CO3 solution (2 M, 1.61 mL, 3.21 mmol). The mixture was purged with Argon gas before the addition of PdCl2(dppf) (47.0 mg, 0.0643 mmol). The reaction mixture was stirred at 80° C. for 2 h. After cooling to rt, water (50 mL) was added and the mixture was extracted with DCM (2×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc/heptane (3:2 v/v) to obtain compound 19a as a yellow solid (276 mg, 87% yield). Mass Spectrum (LCMS, ESI pos.): Calcd. for C25H31N7O4: 494.2 (M+H). Found 494.2.

Workup

  1. temperatureAfter cooling to rt
  2. extractionthe mixture was extracted with DCM (2×50 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with EtOAc/heptane (3:2 v/v)

Sources & evidence

ORD record
ord-2266c23e5a6d4d2b8b3268ad57bcc730
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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