Propargyl alcohol → HCID 9947411, compound

HRID 1070598Notes

Reaction equation

HRID 1070598 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:15](=[O:16])[N:14]3[CH:17]=[C:18](I)[CH:19]=[CH:20][C:13]3=[N:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1.CCN(CC)CC.[CH2:31]([OH:34])[C:32]#[CH:33]>CN(C=O)C.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>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:15](=[O:16])[N:14]3[CH:17]=[C:18]([C:33]#[C:32][CH2:31][OH:34])[CH:19]=[CH:20][C:13]3=[N:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 22397248HCID 22397248, compound

Product 1

HCID 9947411HCID 9947411, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of N-(4-chlorobenzyl)-7-iodo-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamide (Procedure 3, 500 mg), PdCl2(PPh3)2 (21 mg), and Et3N (0.73 mL) in anhydrous DMF (3 mL) is added propargyl alcohol (0.094 mL). The mixture is heated at 90° C. for 1 h, then allowed to cool to room temperature. The reaction mixture is placed under high vacuum to remove the DMF. The resulting solid is dissolved in CH2Cl2 and washed with water. The aqueous layer is extracted with CH2Cl2 (2×). The combined organic layers are dried (Na2SO4), filtered, and condensed to afford a solid. The crude solid is adsorbed onto silica and chromatographed (1% MeOH/CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), and 2% MeOHICH2Cl2 (1.5 L)). Product-containing fractions are combined and concentrated to afford 243 mg (58%) of the title compound as a creme solid. Physical characteristics: m.p. 179-181° C.; 1H NMR (300 MHz, DMSO-d6) δ9.34, 9.07, 9.00, 8.10, 7.85, 7.36, 5.50, 4.54, 4.36; IR (drift) 3294, 1676, 1632, 1618, 1561, 1541, 1521, 1490, 1353, 1335, 1131, 1061, 1040, 842, 797 cm−1; MS (ESI+) m/z 368 (M+H)+; Anal. found: C, 61.96; H, 3.69; N, 11.44.

Workup

  1. temperatureto cool to room temperature
  2. customto remove the DMF
  3. dissolutionThe resulting solid is dissolved in CH2Cl2
  4. washwashed with water
  5. extractionThe aqueous layer is extracted with CH2Cl2 (2×)
  6. dry with materialThe combined organic layers are dried (Na2SO4)
  7. filtrationfiltered
  8. customcondensed
  9. customto afford a solid
  10. customchromatographed (1% MeOH/CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), and 2% MeOHICH2Cl2 (1.5 L))
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-a9433a3cea7d4d598fb8d4e3cf90cfcb
Source dataset
uspto-grants-2005_06
Patent number
US06903097B2

Reaction notes

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