N,N,N',N'-Tetramethylethylenediamine → HCID 86718200, compound

HRID 1624132Notes

Reaction equation

HRID 1624132 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:22][CH2:23][C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])[C:5]2[N:6]([C:8]([C:12]([NH:14][C@H:15]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.[CH3:32][N:33](C)CCN(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>CN(C=O)C.C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N>[C:32]([C:2]1[CH:3]=[C:4]([O:22][CH2:23][C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])[C:5]2[N:6]([C:8]([C:12]([NH:14][C@H:15]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1)#[N:33]

Participants

7

Reactant 3

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86718201HCID 86718201, compound

Product 1

HCID 86718200HCID 86718200, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

Under argon, 500 mg (1.0 mmol) of 6-bromo-8-[(2,6-difluorobenzyl)oxy]-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide, 70.9 mg of zinc(II) cyanide (0.6 mmol, 0.6 equivalents), 30.4 μl of 1,2-bis(dimethylamino)ethane (TMEDA; 0.2 mmol, 0.2 equivalents), 65 mg of tris(dibenzylideneacetone)dipalladium Pd2 dba3 (0.07 mmol, 7 mol %) and 29 mg of xantphos ligand (0.05 mmol, 5 mol %) were dissolved in 2 ml of DMF and, divided into 5 microwave reaction vessels, heated at 160° C. for 5 min (CEM Discovery microwave, 300 Watt irratiation). The combined reaction mixtures were diluted with ethyl acetate and filtered through kieselguhr. The filter cake was washed thoroughly and the filtrate was washed with water, dried over magnesium sulphate, filtered and concentrated. The residue was chromatographed on a 50 g silica gel cartridge (Biotage Isolera, cyclohexane/ethyl acetate gradient as mobile phase). This gave 289 mg of the target compound (64% of theory).

Workup

  1. customdivided into 5 microwave reaction vessels
  2. customThe combined reaction mixtures
  3. filtrationfiltered through kieselguhr
  4. washThe filter cake was washed thoroughly
  5. washthe filtrate was washed with water
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed on a 50 g silica gel cartridge (Biotage Isolera, cyclohexane/ethyl acetate gradient as mobile phase)

Sources & evidence

ORD record
ord-668de4a465b14d25a1aa261d260f38fa
Source dataset
uspto-grants-2014_07
Patent number
US08778964B2

Reaction notes

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