N,N,N',N'-Tetramethylethylenediamine → HCID 59149716, compound

HRID 1675006Notes

Reaction equation

HRID 1675006 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:17]=[CH:18][C:19]4[N:20]([C:22]([C:25]([F:28])([F:27])[F:26])=[N:23][N:24]=4)[N:21]=3)[CH2:12][CH2:11]2)[CH3:9])=[CH:4][CH:3]=1.[CH3:29][N:30](C)CCN(C)C>CN(C=O)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[F:26][C:25]([F:28])([F:27])[C:22]1[N:20]2[N:21]=[C:16]([N:13]3[CH2:14][CH2:15][N:10]([C@@H:8]([C:5]4[CH:6]=[CH:7][C:2]([C:29]#[N:30])=[CH:3][CH:4]=4)[CH3:9])[CH2:11][CH2:12]3)[CH:17]=[CH:18][C:19]2=[N:24][N:23]=1

Participants

7

Reactant 2

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 59149841HCID 59149841, compound

Product 1

HCID 59149716HCID 59149716, compoundYield 380.5%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

6-[4-[(1R)-1-(4-Bromophenyl)ethyl]piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (obtained as described in Example 306) (250 mg, 0.55 mmol), zinc cyanide (38.7 mg, 0.33 mmol), tris(dibenzylideneacetone)dipalladium(0) (5.0 mg, 5.49 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (6.3 mg, 10.98 μmol) and N,N,N′,N′-tetramethylethylenediamine (0.017 mL, 0.11 mmol) were suspended in DMF (2.5 mL) and sealed into a microwave tube. The reaction was heated to 160° C. for 5 minutes in a microwave reactor and cooled to ambient temperature. The resulting mixture was applied to an SCX column and eluted with methanol followed by 2M ammonia in methanol. Fractions containing product were combined and evaporated then purified by preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 4-[(1R)-1-[4-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl]ethyl]benzonitrile (168 mg, 76%) as a colourless solid.

Workup

  1. customsealed into a microwave tube
  2. temperaturecooled to ambient temperature
  3. washeluted with methanol
  4. additionFractions containing product
  5. customevaporated
  6. customthen purified by preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length)
  7. additionFractions containing the desired compound
  8. customwere evaporated to dryness

Sources & evidence

ORD record
ord-de9a53c519ce48eca7a267f9c5ff4ab2
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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