Propargyl alcohol → HCID 86686628, compound

HRID 1850526Notes

Reaction equation

HRID 1850526 reaction equation
Br[C:2]1[C:3]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([CH3:20])([CH3:19])[C:17]#[N:18])=[CH:12][CH:11]=2)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH2:39]([OH:42])[C:40]#[CH:41]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1COCC1>[Cl:8][C:5]1[N:4]=[C:3]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([CH3:20])([CH3:19])[C:17]#[N:18])=[CH:12][CH:11]=2)[C:2]([C:41]#[C:40][CH2:39][OH:42])=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 7859Propargyl alcoholHCID 2724141Tetrabutylammonium FluorideHCID 86686627HCID 86686627, compound

Product 1

HCID 86686628HCID 86686628, compound

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

2-(4-(5-bromo-2-chloropyrimidin-4-ylamino)phenyl)-2-methylpropanenitrile (1.4 gm, 3.98 mmol), bis(triphenylphosphine) palladium(II) chloride (0.14 gm, 0.2 mmol), tetrabutyl ammonium fluoride (2.6 gm, 9.95 mmol) and propargyl alcohol (0.357 mL, 5.97 mmol) were combined into 12 mL THF in a screw cap high pressure vessel and heated in a 70° C. oil bath. After 2 hr the reaction appeared complete by LC/MS. Volatiles were removed and the residue taken up into EtOAc. Organic layer was filtered to remove insoluble soot. Organic layer was washed with water, brine and then dried over sodium sulfate. Volatiles were removed and the residue purified by NPLC (10-75% EtOAc in Heptane, Analogix). (869 mg, 67%). MS m/z 327.4 (M+H)

Workup

  1. customcap high pressure vessel
  2. customVolatiles were removed
  3. filtrationOrganic layer was filtered
  4. customto remove insoluble soot
  5. washOrganic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. customVolatiles were removed
  8. customthe residue purified by NPLC (10-75% EtOAc in Heptane, Analogix)

Sources & evidence

ORD record
ord-568a230289be4cf2a7579db3ae66a8d2
Source dataset
uspto-grants-2015_02
Patent number
US08957074B2

Reaction notes

Loading…