Dimethylformamide → HCID 46842454, compound

HRID 1846374Notes

Reaction equation

HRID 1846374 reaction equation
[CH2:1]([OH:4])[C:2]#[CH:3].[CH:5]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2C(=O)C3[C:18](=[CH:19][CH:20]=[CH:21]C=3)[N:17]=[C:16]2[C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:33](=O)[C:34](F)(F)F)=[C:28](I)[CH:27]=2)=[CH:11][CH:10]=1)([CH2:7][CH3:8])[CH3:6].CN([CH:43]=[O:44])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>[CH:5]([C:9]1[CH:10]=[CH:11][C:12]([N:15]2[C:1](=[O:4])[C:2]3[C:18](=[CH:19][CH:20]=[CH:21][CH:3]=3)[N:17]=[C:16]2[C:26]2[CH:27]=[C:28]3[C:29](=[CH:30][CH:31]=2)[NH:32][C:33]([CH2:43][OH:44])=[CH:34]3)=[CH:13][CH:14]=1)([CH2:7][CH3:8])[CH3:6]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 7859Propargyl alcoholHCID 86659825HCID 86659825, compound

Product 1

HCID 46842454HCID 46842454, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
60 °C

Procedure

Propargyl alcohol (0.045 mL, 0.76 mmol) and PdCl2(PPh3)2 (0.007 g, 0.01 mmol) were added to a solution of N-(4-(3-(4-sec-butylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)-2-iodophenyl)-2,2,2-trifluoroacetamide (0.300 g, 0.51 mmol) in TEA (10 mL) and DMF (3 mL). After heating to 60° C. for 5 hours, the reaction mixture was concentrated in vacuo. The residue was dissolved in EtOAc, washed with saturated NaHCO3, then brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 20% to 80% EtOAc in heptane, plus further purification by flash chromatography on silica gel, eluting with 10% to 50% EtOAc in CH2Cl2, afforded the title compound as a white solid (0.065 g, 29%). 1H-NMR (300 MHz, DMSO-d6): δ11.09 (s, 1H), 8.18 (d, J=7.1 Hz, 1H), 7.87-7.90 (m, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.47-7.64 (m, 2H), 6.93-7.25 (m, 6H), 6.19 (s, 1H), 5.23 (t, J=5.6 Hz, 1H), 4.54 (d, J=5.5 Hz, 2H), 2.53-2.61 (m, 1H), 1.30-1.62 (m, 2H), 1.12 (d, J=6.9 Hz, 3H), 0.63 (t, J=7.2 Hz, 3H). MS (APCI) m/z: 424 (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc
  3. washwashed with saturated NaHCO3
  4. dry with materialbrine, dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography on silica gel
  8. washeluting with 20% to 80% EtOAc in heptane, plus further purification by flash chromatography on silica gel
  9. washeluting with 10% to 50% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-1bb68cf340444ed999c456ca513497d3
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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