Ethanol → Tert-Butyl 4-{N-[(6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta-[g]quinazolin-6yl]amino}-2-fluorobenzoate

HRID 490157Notes

Reaction equation

HRID 490157 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14]#[N:15])[CH:10]([NH:16][C:17]1[CH:29]=[CH:28][C:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[C:19]([F:30])[CH:18]=1)[CH2:9][CH2:8]2)(=O)[CH3:2].C([OH:33])C.OO.[OH-].[Na+]>O>[CH3:2][C:1]1[NH:15][C:14](=[O:33])[C:13]2[C:5](=[CH:6][C:7]3[CH2:8][CH2:9][CH:10]([NH:16][C:17]4[CH:29]=[CH:28][C:20]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])=[C:19]([F:30])[CH:18]=4)[C:11]=3[CH:12]=2)[N:4]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 67363698Tert-butyl 4-[N-(5-acetamido-6-cyanoindan-1-yl)amino]-2-fluorobenzoate

Product 1

HCID 136065298Tert-Butyl 4-{N-[(6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta-[g]quinazolin-6yl]amino}-2-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of tert-butyl 4-[N-(5-acetamido-6-cyanoindan-1-yl)amino]-2-fluorobenzoate (0.182 g, 0.44 mmol), ethanol (2 ml), and water (0.4 ml) was cooled in an ice-bath, then 30% aqueous H2O2 solution (0.37 ml) was added followed by granulated sodium hydroxide pellets (0.030 g, 0.75 mmol). The reaction mixture was stirred at ˜0° C. for 10 min, then it was placed in an oil bath preheated to 55° C. and stirred at this temperature for 30 min The reaction mixture was allowed to cool to room temperature, then the solvents were removed in vacuo and the residue was suspended in water (˜15 ml). The pH of this mixture was adjusted to ˜4 with 1N hydrochloric acid. The white precipitate was collected by filtration, washed with water, and dried in vacuo over P2O5. The desired compound was obtained as a white solid 0.155 g (85%), m.p. 150-152° C.; 1H-N (250 MHz, DMSO-d6, TMS) 1.50 (s, 9H, C(C3)3), 2.32 (s, 3H, 2-CH3), 1.83, 2.53 (2×m, 2H, 7-H), 3.00 (m, 2H, 8-H), 5.15 (q, J=7.40 Hz, 1H, 6-H), 6.57 (m, 2H, 3′,5′-H), 7.16 (d, J=7.75 Hz, 1H, N10—H), 7.44, 7.87 (2×s, each 1H, 5-H, 9-H), 7.59 (t, J=8.73 Hz, 6′-H), 12.11 (s, 1H, N3-H), MS (ESI, m/z) 819 {(2M+H)+, 100%}, 432 {(M+Na)+, 10%}, 410 {M+H)+, 15%}; Found: C, 66.81; H, 5.89, N, 10.11; F, 4.58; C23H24FN3O30.25H2O requires C, 66.74; H, 5.96; N, 10.15%; F, 4.59%.

Workup

  1. temperaturewas cooled in an ice-bath
  2. customit was placed in an oil bath
  3. custompreheated to 55° C.
  4. stirringstirred at this temperature for 30 min The reaction mixture
  5. temperatureto cool to room temperature
  6. customthe solvents were removed in vacuo
  7. filtrationThe white precipitate was collected by filtration
  8. washwashed with water
  9. dry with materialdried in vacuo over P2O5

Sources & evidence

ORD record
ord-3d09471dd5e6454b95f5258cc68e29a5
Source dataset
uspto-grants-2009_05
Patent number
US07528141B2

Reaction notes

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