Diisopropylethylamine → HCID 11472787, compound

HRID 495214Notes

Reaction equation

HRID 495214 reaction equation
CCN(C(C)C)C(C)C.[CH2:10]([C:12]1[C:16](I)=[C:15]([CH:18]=[O:19])[NH:14][C:13]=1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH3:11].[C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1)#[CH:28]>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.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].[Cu]I>[CH2:10]([C:12]1[C:16]([C:28]#[C:27][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[C:15]([CH:18]=[O:19])[NH:14][C:13]=1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH3:11]

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 137268EthynylpyridineHCID 11348633HCID 11348633, compound

Product 1

HCID 11472787HCID 11472787, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Tert-butyl 3-ethyl-5-formyl-4-iodo-1H-pyrrole-2-carboxylate was obtained following the procedures described in Example 1. Pd(Pt-Bu3)2 (7.0 mg, 0.010 mmol), Pd2(dba)3 (6.0 mg, 0.010 mmol), and CuI (2.0 mg, 0.010 mmol) were combined in a dry flask under N2 prior to evacuating the flask and refilling with argon. After the flask was charged with dioxane (2.0 mL) it was sparged with argon prior to the sequential addition of i-Pr2NEt (0.0259 mL, 0.19 mmol), a solution of tert-butyl 3-ethyl-5-formyl-4-iodo-1H-pyrrole-2-carboxylate (56.0 mg, 0.16 mmol) in dioxane (1.0 mL), and 2-ethynylpyridine (0.0194 mL, 0.19 mmol). The reaction was heated to 80° C. until complete consumption of the starting material. After the reaction was cooled to ambient temperature, it was filtered through a plug of silica gel and concentrated in vacuo. The resultant residue was dissolved in acetonitrile and purified by reverse phase HPLC. Proton NMR for the product was consistent with the title compound. 1H NMR (500 MHz, CDCl3) δ 10.23 (s, 1H); 3.10 (q, J=7.3 Hz, 2H); 1.61 (s, 9H); 1.16 (t, J=7.3 Hz, 3H). HRMS (ES) exact mass calculated for C21H21F3N2O5 (M+H+): 325.1547. Found 325.1549.

Workup

  1. customto evacuating the flask
  2. additionAfter the flask was charged with dioxane (2.0 mL) it
  3. customwas sparged with argon
  4. temperatureAfter the reaction was cooled to ambient temperature
  5. filtrationit was filtered through a plug of silica gel
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resultant residue was dissolved in acetonitrile
  8. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-84989590a1404fda9a63a46e1f35ba78
Source dataset
uspto-grants-2009_05
Patent number
US07538231B2

Reaction notes

Loading…