Sodium Carbonate → HCID 67368383, compound

HRID 1910967Notes

Reaction equation

HRID 1910967 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[N:8]3[CH2:11][CH2:12][NH:13][C:7]3([C:14]3[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=3)[CH2:6][N:5]2[CH:21]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:20][C:17]1[N:18]=[CH:19][C:14]([C:7]23[NH:13][CH2:12][CH2:11][N:8]2[C:9](=[O:10])[C:4]2[N:5]([CH:21]=[C:2]([C:24]4[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=4)[CH:3]=2)[CH2:6]3)=[N:15][CH:16]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acid2×HCID 67366902HCID 67366902, compound

Product 1

HCID 67368383HCID 67368383, compoundYield 76%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 7-bromo-10a-(5-methylpyrazin-2-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (20 mg, 0.057 mmol), 3-pyridylboronic acid (9 mg, 0.073 mg) in 1,2-dimethoxyethane (0.5 mL) was added a solution of sodium carbonate (16 mg, 0.19 mmol) in water (0.15 mL) and ethanol (0.1 mL). The mixture was flushed with argon and dichlorobis(triphenylphosphine)palladium(II) (3.5 mg, 5×10−3 mmol) was added. The mixture was further degassed with argon, sealed and heated at 100° C. overnight. The following day an additional batch of 3-pyridylboronic acid (20 mg, 0.16 mmol) and dichlorobis(triphenylphosphine)palladium(II) (4 mg, 5.7×10−3 mmol) were added. The mixture was degassed, sealed and heated at 100° C. After 3 hours the reaction was complete. The mixture was then concentrated and purified by flash chromatography (Biotage SP4, gradient 1CV CH2Cl2, 0-10% MeOH in CH2Cl2 and hold 10% MeOH) to give 10a-(5-methylpyrazin-2-yl)-7-(pyridin-3-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (15 mg, yield: 76%). 1H-NMR (400 MHz, CDCl3): δ 2.53 (s, 3H), 2.99 (dt, 1H, J 7.9 Hz), 3.35 (ddd, 1H, J 10.9, 7.5, 3.7 Hz), 3.77 (ddd, 1H, J 11.2, 7.6, 3.8 Hz), 4.00 (dt, 1H, J 11.1, 7.8 Hz), 4.26 (d, 1H, J 12.0 Hz), 4.87 (d, 1H, J 12.0 Hz), 6.87 (d, 1H, J 1.7 Hz), 7.20-7.25 (m, 2H), 7.66-7.70 (m, 1H), 8.37-8.44 (m, 3H), 8.68 (d, 1H, J 1.8 Hz).

Workup

  1. additionwas added
  2. customThe mixture was further degassed with argon
  3. customsealed
  4. customThe mixture was degassed
  5. customsealed
  6. temperatureheated at 100° C
  7. concentrationThe mixture was then concentrated
  8. custompurified by flash chromatography (Biotage SP4, gradient 1CV CH2Cl2, 0-10% MeOH in CH2Cl2 and hold 10% MeOH)

Sources & evidence

ORD record
ord-e30a8c1cc119422790fd07adf3c76715
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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