Sodium Carbonate → HCID 86727124, compound

HRID 1054490Notes

Reaction equation

HRID 1054490 reaction equation
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[CH:11][C:10](B2OC(C)(C)C(C)(C)O2)=[CH:9][N:8]=1.Cl[C:23]1[N:28]=[C:27]([NH2:29])[CH:26]=[N:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:8]=[CH:9][C:10]([C:23]2[N:28]=[C:27]([NH2:29])[CH:26]=[N:25][CH:24]=2)=[CH:11][N:12]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 1184582-Amino-6-ChloropyrazineHCID 71260733HCID 71260733, compound

Product 1

HCID 86727124HCID 86727124, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A flask was charged with (S)-2-(2-methylpyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (7.1 g, 24.55 mmol), 6-chloropyrazin-2-amine (2.89 g, 22.32 mmol), Pd(PPh3)4 (2.58 g, 2.232 mmol) and 1,4-dioxane (74.4 mL). The reaction mixture was purged with nitrogen for several minutes before aqueous 2M sodium carbonate (22.32 mL, 44.6 mmol) solution was added. The reaction mixture was then purged with nitrogen for another 10 minutes at 25° C. before it was heated to 90° C. under nitrogen overnight. 1,4-Dioxane was removed in vacuo and the crude mixture was diluted with EtOAc. The product was washed with water and brine. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified on silica gel chromatography to yield 3.38 g (13.2 mmol, 84%) of the title product as a light brown solid. ESI-MS (EI+, m/z): 258.26, 1H NMR (Chloroform-d) δ: 8.92 (d, J=5.3 Hz, 2H), 8.25 (s, 1H), 7.88 (s, 1H), 4.60 (s, 2H), 4.39 (d, J=5.8 Hz, 1H), 3.81-3.68 (m, 1H), 3.68-3.55 (m, 1H), 2.24-1.95 (m, 3H), 1.78 (s, 1H), 1.31 (d, J=6.3 Hz, 3H)

Workup

  1. additionwas added
  2. customThe reaction mixture was then purged with nitrogen for another 10 minutes at 25° C. before it
  3. custom1,4-Dioxane was removed in vacuo
  4. additionthe crude mixture was diluted with EtOAc
  5. washThe product was washed with water and brine
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified on silica gel chromatography

Sources & evidence

ORD record
ord-77b12f4c6c184bc59ac79514ffd12b8a
Source dataset
uspto-grants-2016_07
Patent number
US09394308B2

Reaction notes

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