Hydrochloric Acid → HCID 68595001, compound

HRID 220588Notes

Reaction equation

HRID 220588 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+].CC1(C)C(C)(C)OB([C:36]2[CH:41]=[CH:40][C:39]([CH2:42][C:43]([NH2:45])=[O:44])=[CH:38][CH:37]=2)O1.Cl>CN(C)C(=O)C.C(#N)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.O>[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:41]=[CH:40][C:39]([CH2:42][C:43]([NH2:45])=[O:44])=[CH:38][CH:37]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[CH:16]=[N:17]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 594382163'-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylHCID 667094992-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide

Product 1

HCID 68595001HCID 68595001, compoundYield 37.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 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-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetamide (313 mg, 1.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.0050 g, 0.0058 mmol), then water (2 mL) and degas with nitrogen for 5 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 using silica gel chromatography (eluting with 5:95 to 20:80 methanol:DCM) to give an oil. 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 (0.165 g, 37%). MS (ES): m/z=406 [M+H]+.

Workup

  1. customthen purify by SCX-2® chromatography
  2. washwashing with methanol
  3. washElute with 2 M ammonia in methanol
  4. concentrationconcentrate
  5. customPurify
  6. washsilica gel chromatography (eluting with 5:95 to 20:80 methanol:DCM)
  7. customto give an oil

Sources & evidence

ORD record
ord-e21806123db34104966e78d6565ba81e
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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