Tetrahydrofuran → (+/-)-2-(bicyclo[2.1.1]hex-2-yl)-N-[4-oxo-2-(propan-2-yl)quinazolin-3(4H)-yl]acetamide

HRID 1912523Notes

Reaction equation

HRID 1912523 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[CH:13]([CH3:15])[CH3:14].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C([O:37][CH2:38][CH3:39])(=O)C.C(N([CH2:45][CH3:46])CC)C.O1[CH2:51][CH2:50][CH2:49][CH2:48]1>>[CH:46]12[CH2:45][CH:50]([CH2:51]1)[CH2:49][CH:48]2[CH2:39][C:38]([NH: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[CH:13]([CH3:15])[CH3:14])=[O:37]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 51882113-Amino-2-isopropyl-4(3H)-quinazolinone

Product 1

HCID 68751316(+/-)-2-(bicyclo[2.1.1]hex-2-yl)-N-[4-oxo-2-(propan-2-yl)quinazolin-3(4H)-yl]acetamide

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-amino-2-isopropylquinazolin-4(3H)-one (Aldrich, 80 mg, 0.4 mmol) and Example 22C (55 mg, 0.4 mmol) in tetrahydrofuran (5 mL) was added a solution of 1-propanephosphonic acid cyclic anhydride (Aldrich, 50% w/w in ethyl acetate (0.7 mL, 1.2 mmol) followed by triethylamine (0.16 mL, 1.2 mmol). The reaction was stirred at 80° C. overnight. The reaction was quenched with 1M NaHCO3 (10 mL). The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, 0-50% of ethyl acetate in hexanes) to obtain 65 mg of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.10 (m, 2H), 1.21-1.29 (m, 1H), 1.31 (d, J=6.7 Hz, 3H), 1.36 (d, J=6.7 Hz, 3H), 1.57-1.78 (m, 2H), 1.94-2.07 (m, 1H), 2.42-2.68 (m, 5H), 3.12-3.27 (m, 1H), 7.38-7.50 (m, 1H), 7.65-7.81 (m, 3H), 8.21 (dd, J=8.1, 1.0 Hz, 1H); MS (ESI+) m/z 326 (M+H)+. Elemental Analysis: Calculated for C19H23N3O2: C: C, 70.13; H, 7.12; N, 12.91. Found: C, 70.32; H, 7.10; N, 12.85.

Workup

  1. customThe reaction was quenched with 1M NaHCO3 (10 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (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 (SiO2, 0-50% of ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8ae2eb9f50454226aee5a598ddfdd86f
Source dataset
uspto-grants-2013_12
Patent number
US08609674B2

Reaction notes

Loading…