Water → HCID 68596091, compound

HRID 220587Notes

Reaction equation

HRID 220587 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[N:17][N:18]([CH3:21])[C:19]=3[CH3:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:28][C:29]([C:33]1[CH:38]=[CH:37][C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][CH:34]=1)([CH3:32])[C:30]#[N:31].O>CN(C)C(=O)C.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>[ClH:1].[CH3:21][N:18]1[C:19]([CH3:20])=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[C:2]([C:36]4[CH:37]=[CH:38][C:33]([C:29]([CH3:32])([CH3:28])[C:30]#[N:31])=[CH:34][CH:35]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[CH:16]=[N:17]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 59322050α,α-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzeneacetonitrileHCID 594382163'-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Product 1

HCID 68596091HCID 68596091, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

Dissolve 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (307 mg, 1.0 mmol) in N,N-dimethylacetamide (4 mL). Add potassium carbonate (332 mg, 2.4 mmol), 2-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionitrile (300 mg, 1.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.0050 g, 0.0058 mmol), then water (2 mL) and degas with nitrogen for 10 min. Heat at 120° C. for 20 hr., then purify by SCX-2® chromatography washing with methanol. Elute with 2 M ammonia in methanol and concentrate. Purify by low pH reverse phase HPLC, then form the free base by passing through an SCX-2® ion exchange cartridge washing with methanol then eluting with 2 M ammonia in methanol and concentrate. Dissolve the free base in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize to give the title compound as a light yellow powder (158 mg, 35%). MS (ES): m/z=416 [M+H]+.

Workup

  1. custom, then purify by SCX-2® chromatography
  2. washwashing with methanol
  3. washElute with 2 M ammonia in methanol
  4. concentrationconcentrate
  5. customPurify by low pH reverse phase HPLC
  6. customform the free base
  7. washwashing with methanol
  8. washthen eluting with 2 M ammonia in methanol
  9. concentrationconcentrate
  10. dissolutionDissolve the free base in acetonitrile
  11. additionby adding 2 M aq HCl solution

Sources & evidence

ORD record
ord-08868d7810924327b6e6b5612e5f4bc3
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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