Propargyl alcohol → HCID 66977283, compound

HRID 712328Notes

Reaction equation

HRID 712328 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([N:11]3[CH2:16][N:15]([CH3:17])[CH2:14][N:13]([CH2:18][CH3:19])[C:12]3=[O:20])=[N:7][C:6]=2[CH:5]=[C:4]([C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:32][CH2:31][C:30]([CH2:38][CH3:39])([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:29][CH2:28]3)=[N:25][CH:26]=2)[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[CH2:66]([OH:69])[C:67]#[CH:68]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C=O)C>[CH2:38]([C:30]1([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:29][CH2:28][N:27]([C:24]2[N:23]=[CH:22][C:21]([C:4]3[CH:3]=[C:2]([C:68]#[C:67][CH2:66][OH:69])[C:10]4[S:9][C:8]([N:11]5[CH2:16][N:15]([CH3:17])[CH2:14][N:13]([CH2:18][CH3:19])[C:12]5=[O:20])=[N:7][C:6]=4[CH:5]=3)=[CH:26][N:25]=2)[CH2:32][CH2:31]1)[CH3:39]

Participants

8

Reactant 4

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 66977160HCID 66977160, compound

Product 1

HCID 66977283HCID 66977283, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl 1-[5-[7-bromo-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylate (700 mg, 1.14 mmol), PdCl2(PPh3)2 (32 mg, 0.05 mmol) and triphenylphosphine (3 mg, 0.01 mmol) were placed in a 10-20 mL microwave vial and anhydrous DMF (14 mL) added, quickly followed by triethylamine (0.95 mL, 6.81 mmol) and propargyl alcohol (0.13 mL, 2.27 mmol). The solution was bubbled with argon for ˜3 minutes then CuI (4 mg, 0.02 mmol) was added. The vial was capped and mixture degassed then heated in the microwave at 100° C. for 30 minutes. More PdCl2(PPh3)2 (11 mg) and propargyl alcohol (0.05 mL) were added and argon was bubbled through the mixture then CuI (1.5 mg) added. The vial was capped and mixture degassed then heated in the microwave again at 100° C. for 15 minutes. The crude reaction mixture was filtered through a PTFE filter. The filter was rinsed with EtOAc and then water. The filtrate was diluted with water, extracted into EtOAc (4×60 mL) and the combined organic layers washed with water (2×50 mL) and brine, dried over Na2SO4 and concentrated to dryness under reduced pressure to give a brown solid. The mixture was purified by chromatography, Biotage SP4, 40 g Si cartridge, 50-80% EtOAc in cyclohexane and the relevant fractions combined to give the desired product as an off-white solid, 247 mg (37%). MS: 592.13 [M+H]+.

Workup

  1. customThe solution was bubbled with argon for ˜3 minutes
  2. customThe vial was capped
  3. custommixture degassed
  4. additionMore PdCl2(PPh3)2 (11 mg) and propargyl alcohol (0.05 mL) were added
  5. customargon was bubbled through the mixture
  6. additionCuI (1.5 mg) added
  7. customThe vial was capped
  8. custommixture degassed
  9. temperaturethen heated in the microwave again at 100° C. for 15 minutes
  10. customThe crude reaction mixture
  11. filtrationwas filtered through a PTFE
  12. filtrationfilter
  13. washThe filter was rinsed with EtOAc
  14. additionThe filtrate was diluted with water
  15. extractionextracted into EtOAc (4×60 mL)
  16. washthe combined organic layers washed with water (2×50 mL) and brine
  17. dry with materialdried over Na2SO4
  18. concentrationconcentrated to dryness under reduced pressure
  19. customto give a brown solid
  20. customThe mixture was purified by chromatography, Biotage SP4, 40 g Si cartridge, 50-80% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-4da27372a25544dc987fb756af305d6a
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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