Sodium Carbonate → (S)-6-(2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyrazin-2-amine

HRID 1054487Notes

Reaction equation

HRID 1054487 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:27][CH2:26][CH2:25][C@H:24]3[C:28]([F:31])([F:30])[F:29])=[N:21][CH:22]=2)O1.O1CCOCC1.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.CO>[F:31][C:28]([F:29])([F:30])[C@@H:24]1[CH2:25][CH2:26][CH2:27][N:23]1[C:20]1[N:19]=[CH:18][C:17]([C:2]2[N:7]=[C:6]([NH2:8])[CH:5]=[N:4][CH:3]=2)=[CH:22][N:21]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 1184582-Amino-6-ChloropyrazineHCID 86727118(S)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidine

Product 1

HCID 86727123(S)-6-(2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyrazin-2-amineYield 68.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

A round bottom flask was charged with 6-chloropyrazin-2-amine (0.401 g, 3.09 mmol), (S)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidine (1.062 g, 3.09 mmol), Pd(PPh3)4 (0.358 g, 0.309 mmol) and 1,4-Dioxane (Volume: 7.74 ml). The reaction mixture was purged with nitrogen for several minutes before an aqueous 2M sodium carbonate (3.09 ml, 6.19 mmol) was added. The reaction mixture was purged for another 10 minutes under nitrogen before it was placed in a 90° C. oil bath and allowed to stir overnight. 1,4-Dioxane was removed in vacuo and the crude mixture was diluted with EtOAc. The product was wash with water (3×) and brine. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified on silica gel using normal phase flash chromatography, eluting with CH2Cl2:MeOH to yield 0.655 g (2.11 mmol, 68.2%) of the title product; 1H NMR (300 MHz, DMSO-d6) δ 9.01 (s, 2H), 8.26 (s, 1H), 7.83 (s, 1H), 6.55 (s, 2H), 5.16-5.02 (m, 1H), 3.77-3.60 (m, 2H), 2.29-2.01 (m, 4H); m/z [M+H]+=311.12

Workup

  1. additionwas added
  2. customThe reaction mixture was purged for another 10 minutes under nitrogen before it
  3. customwas placed in a 90° C.
  4. custom1,4-Dioxane was removed in vacuo
  5. additionthe crude mixture was diluted with EtOAc
  6. washThe product was wash with water (3×) and brine
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified on silica gel using normal phase flash chromatography
  11. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-0d426b17f8c24c0784bddb982cfafb6a
Source dataset
uspto-grants-2016_07
Patent number
US09394308B2

Reaction notes

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