Cesium acetate → 2-(Hydroxymethyl)-3,6,7,8-tetrahydro-4H-cyclopenta[g]quinazolin-4-one

HRID 490152Notes

Reaction equation

HRID 490152 reaction equation
C([O-])(=[O:3])C.[Cs+].Cl[CH2:7][C:8]1[NH:17][C:16](=[O:18])[C:15]2[C:10](=[CH:11][C:12]3[CH2:21][CH2:20][CH2:19][C:13]=3[CH:14]=2)[N:9]=1>CN(C=O)C>[OH:3][CH2:7][C:8]1[NH:17][C:16](=[O:18])[C:15]2[C:10](=[CH:11][C:12]3[CH2:21][CH2:20][CH2:19][C:13]=3[CH:14]=2)[N:9]=1

Participants

4

Reactant 2

HCID 5152919Cesium acetateHCID 1358097812-(Chloromethyl)-3,6,7,8-tetrahydro-4H-cyclopenta[g]quinazolin-4-one

Product 1

HCID 1360653102-(Hydroxymethyl)-3,6,7,8-tetrahydro-4H-cyclopenta[g]quinazolin-4-oneYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

A solution of caesium acetate (14.4 g, 75.2 mmol) in dry DMF (40 ml) was heated to 60° C. under argon for 30 min. The mixture was cooled to 40° C. and a suspension of 2-chloromethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-4one (L. Skelton, V. Bavetsias, A. Jackman, WO 00/050417-A1; 2.2 g, 9.4 mmol) in dry DMF (60 ml) was added via a cannula. The mixture was heated to 80° C. under argon for 16 h. The mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was suspended in water (50 ml) and MeOH (20 ml). The pH was adjusted to 12.5 with 1 M sodium hydroxide solution and the brown suspension was stirred for 2 h at room temperature. The insoluble brown solid was removed by filtration and the resulting solution was acidified to pH 5 with 1M hydrochloric acid. The precipitate was collected by filtration, washed with acidified water and dried in vacuo over P2O5 to yield the product as a pale yellow solid (1.17 g, 58%); m.p. 205-210° C.; 1H NMR (DMSO-d6) δ 2.07 (quin, J=7.4 Hz, 2H, 7-H), 2.98 (q, J=6.95 Hz, 4H, 6-H and 8-H), 4.38 (s, 2H, 2-CH2), 7.46 (s, 1H, 9-H), 7.92 (s, 1H, 5-H); MS (FAB-m/z): Found 217 [(M+H)+, 100%]; HRMS: measured 217.0977; calculated for C12H13N2O2 (M+H)+: 217.0977; Found C, 64.01; H, 5.23; N, 12.34. C12H13N2O2.½H2O requires C, 63.93; H, 5.77; N, 12.43%.

Workup

  1. temperatureThe mixture was heated to 80° C. under argon for 16 h
  2. temperatureThe mixture was cooled to room temperature
  3. customthe solvent was removed in vacuo
  4. customThe insoluble brown solid was removed by filtration
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with acidified water
  7. dry with materialdried in vacuo over P2O5

Sources & evidence

ORD record
ord-c6e33f96ff5e485caeee8ee252edba81
Source dataset
uspto-grants-2009_05
Patent number
US07528141B2

Reaction notes

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