(4-Fluoro-3-methylphenyl)methanamine → HCID 54747151, compound

HRID 1093140Notes

Reaction equation

HRID 1093140 reaction equation
[CH3:1][N:2]([C:4](=[O:28])[C:5]([N:7]([CH3:27])[C:8]12[CH2:16][CH2:15][CH:12]([CH2:13][CH2:14]1)[CH2:11][N:10]1[C:17](=[O:26])[C:18]([OH:25])=[C:19]([C:21]([O:23]C)=O)[N:20]=[C:9]21)=[O:6])[CH3:3].[F:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][NH2:37])=[CH:32][C:31]=1[CH3:38]>C(O)C>[F:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][NH:37][C:21]([C:19]2[N:20]=[C:9]3[C:8]4([N:7]([CH3:27])[C:5](=[O:6])[C:4]([N:2]([CH3:1])[CH3:3])=[O:28])[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16]4)[CH2:11][N:10]3[C:17](=[O:26])[C:18]=2[OH:25])=[O:23])=[CH:32][C:31]=1[CH3:38]

Participants

4

Reactant 2

HCID 2774599(4-Fluoro-3-methylphenyl)methanamineHCID 57905168HCID 57905168, compound

Product 1

HCID 54747151HCID 54747151, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of methyl 10-(((dimethylamino)(oxo)acetyl)(methyl)amino)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate (3 g, 7.65 mmol) in ethanol (80 mL) was added (4-fluoro-3-methylphenyl)methanamine (2.90 mL, 22.94 mmol) and the mixture was heated at 90° C. for 18 h. The reaction mixture was cooled, concentrated, diluted with ethyl acetate and washed twice with 0.2N NaOH (2×100 mL). The organic layer was discarded and the aqueous layer acidified with conc. HCl and extracted with dichloromethane (2×150 mL), dried (Na2SO4), filtered and concentrated. The crude product was recrystallized from methanol to afford the title compound (2.5 g, 66% yield) as a crystalline white solid. 1H NMR (500 MHz, CDCl3) δ: 12.13 (1 H, s), 9.56 (1 H, brs), 7.20-7.23 (1 H, m), 7.15-7.20 (1 H, m), 6.88-6.93 (1 H, m), 4.83 (1 H, dd, J=15.56, 7.02 Hz), 4.55-4.62 (1 H, m), 4.39-4.45 (1 H, m), 3.60 (1 H, d, J=15.56 Hz), 3.33-3.47 (2 H, m), 3.01 (3 H, s), 2.99 (3H, s), 2.97 (3 H, s), 2.49 (1 H, brs), 2.23 (3 H, d, J=1.83 Hz), 1.97-2.09 (4 H, m), 1.74-1.84 (2 H, m). LCMS (M+H)=500.69. HPLC purity: >95%.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. additiondiluted with ethyl acetate
  4. washwashed twice with 0.2N NaOH (2×100 mL)
  5. extractionextracted with dichloromethane (2×150 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was recrystallized from methanol

Sources & evidence

ORD record
ord-1637772e2d584a6e98fdab29e837caa8
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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