Lithium aluminum hydride → HCID 58204365, compound

HRID 886359Notes

Reaction equation

HRID 886359 reaction equation
[AlH4-].[Li+].[CH:3]([N:6]1[C:10]([C:11]2[N:12]=[C:13]3[C:19]4[CH:20]=[CH:21][C:22]([C:24]([NH2:26])=O)=[CH:23][C:18]=4[O:17][CH2:16][CH2:15][N:14]3[CH:27]=2)=[CH:9][CH:8]=[N:7]1)([CH3:5])[CH3:4]>O1CCCC1>[CH:3]([N:6]1[C:10]([C:11]2[N:12]=[C:13]3[C:19]4[CH:20]=[CH:21][C:22]([CH2:24][NH2:26])=[CH:23][C:18]=4[O:17][CH2:16][CH2:15][N:14]3[CH:27]=2)=[CH:9][CH:8]=[N:7]1)([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 28112Lithium aluminum hydrideHCID 58204657HCID 58204657, compound

Product 1

HCID 58204365HCID 58204365, compoundYield 51.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Lithium tetrahydroaluminate (0.047 g, 1.3 mmol) was suspended in tetrahydrofuran (8 mL) and cooled to 0° C. A solution of 2-(1-isopropyl-1H-pyrazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-9-carboxamide (0.3 g, 0.9 mmol) in tetrahydrofuran (2 mL) was added and the reaction mixture was stirred at cold temperature for 10 min. The flask was gradually brought to room temperature and stirred for 16 h. The reaction was quenched by pouring into a mixture of diethyl ether and saturated aqueous Rochelle's salt solution (1:1). The mixture containing significant emulsion was stirred very vigorously until the phases separated (ca. 2 h). The phases were partitioned and the aqueous layer was extracted numerous times with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated to give (0.15 g, 0.46 mmol) (2-(1-isopropyl-1H-pyrazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)methanamine (MS (ESI+) m/z 323.1 (M+H+), calcd. 323.4) which was dissolved in glacial acetic acid (0.8 mL) and water (5 mL). A solution of potassium cyanate (0.114 g, 1.41 mmol) in water was added dropwise. N,N-dimethylformamide (3 mL) was added to help with dissolution. The resulting reaction mixture was stirred at room temperature for 12 h. Subsequently, the reaction was heated at 50° C. for 3 h. The mixture was cooled to room temperature and filtered to provide 0.02 g (10% yield) of 337. MS (ESI+) m/z 367.1 (M+H+), calcd. 367.4. 1H NMR (400 MHz, DMSO) δ 8.53 (s, 5H), 8.33 (d, J=8.2 Hz, 1H), 7.61 (d, J=3.7 Hz, 1H), 7.43 (s, 1H), 7.01 (d, J=8.7 Hz, 1H), 6.91 (s, 1H), 6.63 (s, 1H), 6.38 (s, 1H), 5.62 (s, 2H), 5.42 (s, 7H), 4.47 (s, 3H), 4.17 (d, J=5.8 Hz, 2H), 1.44 (d, J=6.4 Hz, 6H)

Workup

  1. customwas gradually brought to room temperature
  2. stirringstirred for 16 h
  3. customThe reaction was quenched
  4. additionby pouring into a mixture of diethyl ether and saturated aqueous Rochelle's salt solution (1:1)
  5. additionThe mixture containing significant emulsion
  6. stirringwas stirred very vigorously until the phases
  7. customseparated (ca. 2 h)
  8. customThe phases were partitioned
  9. extractionthe aqueous layer was extracted numerous times with EtOAc
  10. dry with materialThe combined organic layers were dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-af3f7e0eaaa64c7dbc10d0f125545510
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

Loading…