Triethylamine → 4-[[4-[4-[3-[2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethoxy]prop-1-ynyl]-2,6-dimethyl-phenoxy]pyrimidin-2-yl]amino]benzonitrile

HRID 1893145Notes

Reaction equation

HRID 1893145 reaction equation
I[C:2]1[CH:23]=[C:22]([CH3:24])[C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[N:8]=2)=[C:4]([CH3:25])[CH:3]=1.[CH2:26]([O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][OH:41])[C:27]#[CH:28].C(N(CC)CC)C>CN(C=O)C.C1COCC1.C(Cl)Cl.CO.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:41][CH2:40][CH2:39][O:38][CH2:37][CH2:36][O:35][CH2:34][CH2:33][O:32][CH2:31][CH2:30][O:29][CH2:26][C:27]#[C:28][C:2]1[CH:23]=[C:22]([CH3:24])[C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[N:8]=2)=[C:4]([CH3:25])[CH:3]=1

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 159170603,6,9,12-Tetraoxapentadec-14-yn-1-olHCID 585605744-[4-(4-Iodo-2,6-dimethylphenoxy)pyrimidin-2-ylamino]benzonitrile

Product 1

HCID 585605804-[[4-[4-[3-[2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethoxy]prop-1-ynyl]-2,6-dimethyl-phenoxy]pyrimidin-2-yl]amino]benzonitrileYield 85.4%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent2×

Procedure

To a deoxygenated solution of iodopyrimidine 3 (494 mg, 1.12 mmol) and 2-(2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethoxy)ethanol (Veciani, et al., Ibid.) (780 mg, 3.36 mmol) in dry DMF (1.5 mL) and dry THF (3.0 mL) were added successively dry triethylamine (562.0 mg, 5.55 mmol, 0.80 mL), copper (1) iodide (105.7 mg, 0.56 mmol), and tetrakis(triphenylphosphine)palladium (0) (128.3 mg, 0.11 mmol). The reaction mixture was stirred at 25° C. under a nitrogen atmosphere for 3 hours after which TLC (DCM/methanol=3:97) revealed a more polar product and consumption of starting material 3. The mixture was poured into EDTA solution (20 mL, 5%) and the organic product extracted into EtOAc (3×50 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and the solvent evaporated in vacuo to furnish a residue that was subjected to silica-gel column chromatography using DCM/MeOH (95:5) as eluent to produce 4 as a light-brown oil (522.0 mg, 0.956 mmol, 85%).

Workup

  1. customa more polar product and consumption of starting material 3
  2. additionThe mixture was poured into EDTA solution (20 mL, 5%)
  3. extractionthe organic product extracted into EtOAc (3×50 mL)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. customthe solvent evaporated in vacuo
  7. customto furnish a residue that

Sources & evidence

ORD record
ord-aae2c27c736c4215939ec13b1d6033ba
Source dataset
uspto-grants-2013_08
Patent number
US08513205B2

Reaction notes

Loading…