Triphenylphosphine → ABT-072

HRID 1504921Notes

Reaction equation

HRID 1504921 reaction equation
[C:1]([C:5]1[C:6]([O:32][CH3:33])=[C:7]([C:19]#[C:20][C:21]2[CH:26]=[CH:25][C:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[CH:23][CH:22]=2)[CH:8]=[C:9]([N:11]2[CH:16]=[CH:15][C:14](=[O:17])[NH:13][C:12]2=[O:18])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(N(C)C)=O.C([SiH](CC)CC)C>O1CCCC1.C([Pd]Cl)C=C.O>[C:1]([C:5]1[C:6]([O:32][CH3:33])=[C:7]([CH:8]=[C:9]([N:11]2[CH:16]=[CH:15][C:14](=[O:17])[NH:13][C:12]2=[O:18])[CH:10]=1)/[CH:19]=[CH:20]/[C:21]1[CH:26]=[CH:25][C:24]([NH:27][S:28]([CH3:31])(=[O:29])=[O:30])=[CH:23][CH:22]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 12052TriethylsilaneHCID 31374DimethylacetamideHCID 46917481HCID 46917481, compound

Product 1

HCID 57775240ABT-072

Reagents, catalysts & solvents 3

HCID 178455862HCID 178455862, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a flask was successively added N-(4-((3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)ethynyl)phenyl)methanesulfonamide (6) (20 g; 42.60 mmol); allylpalladium(II) chloride (0.39 g; 1.06 mmol); triphenylphosphine (1.12 g; 4.26 mmol) and a solution of dimethylacetamide (80 ml)/water (2.3 ml) previously purge with nitrogen. The solution was heated at 70° C. for 30 minutes. To the reaction mixture was then added over 3 hours triethylsilane (7.42 g; 63.90 mmol). The mixture was stirred for 12 hours at 70° C. The reaction was cooled at 23° C. then diluted with tetrahydrofuran (180 ml) and successively washed with a solution of 1% Cysteine/2.5% NaHCO3/7% NaCl and a solution of 2.5% NaHCO3/7% NaCl. The organic layer was treated with activated carbon and the filtrate was concentrated down and solvent switched to methanol. The slurry was mixed at 62° C. for 60 minutes, cooled down to 25° C., mixed for 2 hours, filtered, and washed with methanol to give the titled compound. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.35 (s, 9 H) 2.99 (s, 3 H) 3.76 (s, 3 H) 5.62 (d, J=7.82 Hz, 1 H) 7.12-7.29 (m, 5 H) 7.51-7.65 (m, 3 H) 7.72 (d, J=7.82 Hz, 1 H) 9.83 (s, 1 H) 11.39 (s, 1 H) MS (APCI) m/z 470.1 (M+H)+.

Workup

  1. customTo a flask was successively added
  2. temperatureThe reaction was cooled at 23° C.
  3. washsuccessively washed with a solution of 1% Cysteine/2.5% NaHCO3/7% NaCl
  4. additionThe organic layer was treated with activated carbon
  5. concentrationthe filtrate was concentrated down
  6. additionThe slurry was mixed at 62° C. for 60 minutes
  7. temperaturecooled down to 25° C.
  8. additionmixed for 2 hours
  9. filtrationfiltered
  10. washwashed with methanol

Sources & evidence

ORD record
ord-3ddd20c979d54fc7820dc1618b844277
Source dataset
uspto-grants-2015_12
Patent number
US09216952B2

Reaction notes

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