Sodium Carbonate → HCID 66937096, compound

HRID 1963916Notes

Reaction equation

HRID 1963916 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[N:4][C:3]=1[C:16]([F:19])([F:18])[F:17].[Cl:20][C:21]1[C:22](B(O)O)=[CH:23][C:24]([F:27])=[N:25][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].B(O)O>COCCOC.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].C(Cl)Cl>[Cl:20][C:21]1[C:22]([C:2]2[N:7]=[C:6]([NH:8][CH2:9][CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[CH:5]=[N:4][C:3]=2[C:16]([F:19])([F:18])[F:17])=[CH:23][C:24]([F:27])=[N:25][CH:26]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 61668Boronic AcidHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 86650630HCID 86650630, compound

Product 1

HCID 66937096HCID 66937096, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

6-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)-5-(trifluoromethyl)pyrazin-2-amine (0.020 g, 0.068 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (0.036 g, 0.203 mmol), and sodium carbonate (0.088 ml, 0.176 mmol, 2 M in H2O) were dissolved in DME (0.70 ml). The solution was then degassed by sparging with argon for 5 min. It was then treated with PdCl2(dppf) CH2Cl2 adduct (0.011 g, 0.014 mmol). The reaction mixture was then heated in a microwave at 110° C. for 25 min. Boronic acid (˜0.036 g, 0.203 mmol) and PdCl2(dppf) CH2Cl2 adduct (˜0.011 g, 0.014 mmol) were added. Heating in the microwave was continued at 110° C. for 25 min. The reaction mixture was then filtered through a pad of Celite. The filtrate was then concentrated in vacuo to give 0.0759 g of crude product. The resulting residue was subjected to silica gel column chromatography. Elution using 25 EtOAc/75 heptane to 100 EtOAc gave 0.0178 g (67%) of 6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)-5-(trifluoromethyl)pyrazin-2-amine. LCMS (m/z): 391.1 (MH+), retention time=0.96 min.

Workup

  1. customThe solution was then degassed
  2. customby sparging with argon for 5 min
  3. temperatureHeating in the microwave
  4. filtrationThe reaction mixture was then filtered through a pad of Celite
  5. concentrationThe filtrate was then concentrated in vacuo
  6. customto give 0.0759 g of crude product
  7. washElution

Sources & evidence

ORD record
ord-036c149d3ae441c0ba399111a77a211b
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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