Methyl iodide → 1-Methyl-2-phenyl-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one

HRID 33287Notes

Reaction equation

HRID 33287 reaction equation
[C:1]1([C:7]2[NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]4[C:19](=[O:20])[NH:18][CH2:17][CH2:16][C:15]=2[C:14]=34)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].I[CH3:24]>C1COCC1.CN1CCCN(C)C1=O>[CH3:24][N:8]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:19](=[O:20])[NH:18][CH2:17][CH2:16][C:15]([C:14]=23)=[C:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 102208822-Phenyl-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one

Product 1

HCID 109567681-Methyl-2-phenyl-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
0 °C

Procedure

A solution of compound 12 (51.3 mg, 0.20 mmol) in THF (1 mL) and 0.1 mL 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) was cooled with an ice/water bath and treated dropwise with a suspension of NaH (0.45 mmol) in THF (0.5 mL). The yellow mixture was allowed to stir at 0° C. for 10 min., and was treated dropwise with a 1M solution of iodomethane in THF (0.22 mL, 0.22 mmol). The mixture was allowed to warm to ambient temperature and stirred for 30 min. The reaction was quenched at 0° C. with saturated aqueous NH4Cl, and extracted with EtOAc (5 mL×3). The organic solution was washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product was purified by radial chromatography (2 mm SiO2; 1-5% MeOH in CH2Cl2) to yield 18 as a white solid, 44.9 mg (81%). mp 254-256° C. (dec.); 1H NMR (DMSO-d6) δ 2.88 (m, 2H), 3.40 (m, 2H), 3.74 (s, 3H), 7.34 (t, 1H, J=7.7 Hz), 7.56 (m, 5H), 7.73 (d, 1H, J=7.7 Hz), 7.80 (d, 1H, J=7.7 Hz), 8.15 (bt, 1H); Anal. (C18H16N2O.0.75 H2O) C, H, N.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 30 min
  3. customThe reaction was quenched at 0° C. with saturated aqueous NH4Cl
  4. extractionextracted with EtOAc (5 mL×3)
  5. washThe organic solution was washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by radial chromatography (2 mm SiO2; 1-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-db5833d9421847f98d66afa97ad428e0
Source dataset
uspto-grants-2008_09
Patent number
US07429578B2

Reaction notes

Loading…