Diisopropylethylamine → 6-[(1-Methoxy-2-methylindolizin-3-yl)carbonyl]-3-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]quinazoline-2,4(1H,3H)-dione

HRID 535444Notes

Reaction equation

HRID 535444 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[OH:34]/[N:35]=[C:36](/[NH2:38])\[CH3:37].[CH3:39][O:40][C:41]1[C:42]([CH3:69])=[C:43]([C:50]([C:52]2[CH:53]=[C:54]3[C:59](=[CH:60][CH:61]=2)[NH:58][C:57](=[O:62])[N:56]([CH2:63][C:64](OC)=O)[C:55]3=[O:68])=[O:51])[N:44]2[C:49]=1[CH:48]=[CH:47][CH:46]=[CH:45]2>CN(C=O)C.O>[CH3:39][O:40][C:41]1[C:42]([CH3:69])=[C:43]([C:50]([C:52]2[CH:53]=[C:54]3[C:59](=[CH:60][CH:61]=2)[NH:58][C:57](=[O:62])[N:56]([CH2:63][C:64]2[O:34][N:35]=[C:36]([CH3:37])[N:38]=2)[C:55]3=[O:68])=[O:51])[N:44]2[C:49]=1[CH:48]=[CH:47][CH:46]=[CH:45]2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 536066422059-22-9HCID 66653305Methyl {6-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetate

Product 1

HCID 565982206-[(1-Methoxy-2-methylindolizin-3-yl)carbonyl]-3-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]quinazoline-2,4(1H,3H)-dioneYield 41.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

0.14 g (0.37 mmol) of HBTU, 0.21 ml (1.23 mmol) of DIEA and then 0.18 g (1.23 mmol) of (1E)-N′-hydroxyethanimidamide are added, under an inert atmosphere at ambient temperature, to 0.1 g (0.25 mmol) of methyl {6-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetate in 5 ml of DMF. The reaction medium is heated at 90° C. for 24 hours. After hydrolysis with water, the reaction medium is extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium hydrogen carbonate and then with water, dried over sodium sulphate, filtered, and then concentrated under reduced pressure. The yellow solid obtained is purified by silica gel column chromatography, elution being carried out with a dichloromethane/methanol (95/5) mixture. 0.046 g of a yellow solid is obtained.

Workup

  1. extractionthe reaction medium is extracted with ethyl acetate
  2. washThe organic phase is washed with a saturated aqueous solution of sodium hydrogen carbonate
  3. dry with materialwith water, dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe yellow solid obtained
  7. customis purified by silica gel column chromatography, elution

Sources & evidence

ORD record
ord-c927bf85d99947f5940efc6ecd6e6a1b
Source dataset
uspto-grants-2014_10
Patent number
US08859544B2

Reaction notes

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