N,N,N',N'-Tetramethylethylenediamine → HCID 86677782, compound

HRID 1499858Notes

Reaction equation

HRID 1499858 reaction equation
[CH3:1][N:2](C)CCN(C)C.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:52]1[C:53]([O:73][CH2:74][CH3:75])=[C:54]([CH:60]([N:62]2[C:66]3=[N:67][CH:68]=[N:69][C:70]([NH2:71])=[C:65]3[C:64]([CH3:72])=[N:63]2)[CH3:61])[CH:55]=[C:56]([Cl:59])[C:57]=1[CH3:58]>CN(C)C=O.[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]>[NH2:71][C:70]1[N:69]=[CH:68][N:67]=[C:66]2[N:62]([CH:60]([C:54]3[C:53]([O:73][CH2:74][CH3:75])=[C:52]([C:57]([CH3:58])=[C:56]([Cl:59])[CH:55]=3)[C:1]#[N:2])[CH3:61])[N:63]=[C:64]([CH3:72])[C:65]=12

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 86677776HCID 86677776, compound

Product 1

HCID 86677782HCID 86677782, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

N,N,N′,N′-Tetramethylethylenediamine (10 μL, 0.07 mmol), zinc cyanide (3 mg, 0.03 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.9 mg, 0.001 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2 mg, 0.003 mmol) was added successively to a solution of 1-[1-(3-bromo-5-chloro-2-ethoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (14 mg, 0.033 mmol, Peak 1 from Example 195, step 4) in N,N-dimethylformamide (0.5 mL) in a microwave tube. The tube was sealed and degassed and refilled with N2 three times, and then heated at 160° C. under microwave irradiation for 400 seconds. The mixture was cooled, filtered and the crude filtrate was purified using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (2.4 mg, 20%). The product was isolated as a single enantiomer. LCMS calculated for C18H20ClN6O (M+H)+: m/z=371.1; Found: 371.2.

Workup

  1. customThe tube was sealed
  2. customdegassed
  3. additionrefilled with N2 three times
  4. temperatureThe mixture was cooled
  5. filtrationfiltered
  6. customthe crude filtrate was purified
  7. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-5768a685f1ae4a068473aab82542b014
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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