Tetrahydrofuran → HCID 49873136, compound

HRID 1853430Notes

Reaction equation

HRID 1853430 reaction equation
[NH2:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]1[CH2:13][CH3:14].[CH3:15][CH2:16][CH2:17]P1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.[C:33](OCC)(=[O:35])C.C(N([CH2:44][CH3:45])CC)C.[O:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1>>[CH2:13]([C:3]1[N:2]([NH:1][C:33]([C:45]23[CH2:44][CH:48]4[CH2:47][CH:16]([CH2:17][CH:50]([CH2:49]4)[O:46]2)[CH2:15]3)=[O:35])[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)[CH3:14]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 5772533-Amino-2-ethylquinazolin-4(3H)-one

Product 1

HCID 49873136HCID 49873136, compound

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-amino-2-ethylquinazolin-4(3H)-one (Aldrich, 150 mg, 0.79 mmol) and Example 54B (144 mg, 0.79 mmol) in tetrahydrofuran (10 mL), a solution of 1-propanephosphonic acid cyclic anhydride (Aldrich, 50% w/w in ethyl acetate (0.6 mL, 0.95 mmol) was added followed by triethylamine (0.22 mL, 1.60 mmol). The reaction mixture was stirred at 80° C. overnight and quenched with 1M NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% of EtOAc in hexanes) to obtain the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.21 (t, J=7.3 Hz, 3 H), 1.64-1.81 (m, 2 H), 1.81-2.07 (m, 8 H), 2.14-2.29 (m, 2 H), 2.51-2.79 (m, 2H), 4.22-4.32 (m, 1 H), 7.49-7.57 (m, 1 H), 7.66 (d, J=7.5 Hz, 1 H), 7.80-7.89 (m, 1 H), 8.09 (dd, J=8.0, 1.2 Hz, 1 H), 10.59 (s, 1 H); MS (ESI+) m/z 354 (M+H)+; Elemental Analysis: Calculated for C20 H23N3O3: C-67.97; H-6.56, N-11.89. Found: C-67.7; H-6.8; N-11.89.

Workup

  1. customquenched with 1M NaHCO3 (10 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (2×20 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-144bba50957947ce8a79984cb23eeccd
Source dataset
uspto-grants-2015_02
Patent number
US08962639B2

Reaction notes

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