Diisopropylamine → 2-Chloro-N-(3-(4-chloroquinazolin-6-yl)prop-2-yn-1-yl)acetamide

HRID 1264063Notes

Reaction equation

HRID 1264063 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][CH2:6][C:7]#[CH:8])=[O:4].[Cl:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](I)[CH:18]=2)[N:13]=[CH:12][N:11]=1.C(NC(C)C)(C)C>C1COCC1.[Cu](I)I.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][CH2:2][C:3]([NH:5][CH2:6][C:7]#[C:8][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][N:11]=[C:10]2[Cl:9])=[O:4]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 5658442-Chloro-N-(prop-2-yn-1-yl)acetamideHCID 111738094-Chloro-6-iodoquinazoline

Product 1

HCID 224843152-Chloro-N-(3-(4-chloroquinazolin-6-yl)prop-2-yn-1-yl)acetamide

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

2-Chloro-N-prop-2-ynyl-acetamide (385mg; 2.93 mmol) and 4-chloro-6-iodoquinazoline (850 mg; 1 equiv.) were dissolved in dry THF and diisopropylamine (296 mg; 0.41 ml; 1 equiv.). To this mixture was added 0.04 equivalents of copper iodide (22 mg) and Pd(PPh3)2Cl2 (82 mg). The reaction was stirred at room temperature under a nitrogen atmosphere overnight (˜20 hrs). The solvent was then removed in vacuo and the residue dissolved in CH2Cl2. This solution was transferred to a separatory funnel and washed with 1×saturated NH4Cl, brine, dried over Na2SO4 and the solvent removed in vacuo. The product was purified by silica gel chromatography eluting with 1:1 hex/EtOAc and collecting fractions with an Rf=0.25. This yielded the 2-Chloro-N-[3-(4-chloro-quinazolin-6-yl)-prop-2-ynyl]-acetamide as an off white solid (454 mg; 53%). 1H NMR (400 MHz; CDCl3) δ 4.12 (2H, s), 4.40 (2H, d, J=5.2 Hz), 7.91-7.93 (1H, dd, J=2, 6.8 Hz), 8.00 (1H, d, J=8.4 Hz), 8.34 (1H, d, J=1.6 Hz), 9.03 (1H, s). Irms (M+): 294.0, 296.0, 298.1.

Workup

  1. customThe solvent was then removed in vacuo
  2. dissolutionthe residue dissolved in CH2Cl2
  3. customThis solution was transferred to a separatory funnel
  4. washwashed with 1×saturated NH4Cl, brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent removed in vacuo
  7. customThe product was purified by silica gel chromatography
  8. washeluting with 1:1 hex/EtOAc
  9. customcollecting fractions with an Rf=0.25

Sources & evidence

ORD record
ord-56119c9378aa462a89ecfa4170dbedd5
Source dataset
uspto-grants-2003_04
Patent number
US06541481B2

Reaction notes

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