Iodoethane → (7bR,11aS)-9-ethyl-N-[2-fluoro-3-(trifluoromethyl)phenyl]-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-amine

HRID 47569

Reaction equation

HRID 47569 reaction equation
[F:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:12][C:13]1[CH:14]=[C:15]2[C:19]3=[C:20]([CH2:22][O:23][CH2:24][CH2:25][N:18]3[C@H:17]3[CH2:26][CH2:27][NH:28][CH2:29][C@@H:16]23)[CH:21]=1.I[CH2:31][CH3:32].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1>[CH2:31]([N:28]1[CH2:27][CH2:26][C@@H:17]2[N:18]3[CH2:25][CH2:24][O:23][CH2:22][C:20]4[CH:21]=[C:13]([NH:12][C:3]5[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([F:10])([F:11])[F:9])[C:2]=5[F:1])[CH:14]=[C:15]([C:19]3=4)[C@@H:16]2[CH2:29]1)[CH3:32]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 10340Sodium CarbonateHCID 60071829(7bR,11aS)-N-[2-fluoro-3-(trifluoromethyl)phenyl]-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-amine

Product 1

HCID 60071885(7bR,11aS)-9-ethyl-N-[2-fluoro-3-(trifluoromethyl)phenyl]-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (7bR,11aS)-N-[2-fluoro-3-(trifluoromethyl)phenyl]-1,2,7b,8,9,10,11,11a-octahydro-4H-[1,4]oxazepino[6,5,4-hi]pyrido[4,3-b]indol-6-amine free base from EXAMPLE 95 (41 mg, 0.1 mmol) in 5 mL tetrahydrofuran was added iodoethane (0.020 mL, 0.22 mmol) and sodium carbonate (21 mg, 0.22 mmol). The reaction was stirred at 60° C. for 3 h and then was cooled, quenched with water, extracted with ethyl acetate, washed with brine, dried (MgSO4) and concentrated. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and the product containing fractions were concentrated, free-based with aq ammonium hydroxide, extracted with chloroform, washed with brine, dried (K2CO3) and concentrated to afford the title compound of EXAMPLE 144. 1H NMR(CDCl3) δ: 7.15 (t, 1H, J=7.3 Hz), 7.05-6.95 (m, 2H), 6.91 (d, 1H, J=1.9 Hz), 6.77 (d, 1H, J=1.8 Hz), 5.73 (d, 1H, J=2.9 Hz), 4.63 (ABq, 2H, JAB=14.3 Hz), 4.25 (app d, 1H, J=12.9 Hz), 3.75 (app t, 1H), 3.43-3.36 (m, 2H), 3.27 (dd, 1H, J=12.8, 2.9 Hz), 2.97-2.80 (m, 2H), 2.75 (app t, 1H), 2.55-2.45 (m, 2H), 2.40-2.30 (m, 1H), 2.15-2.00 (m, 2H), 1.88 (app t, 1H), 1.15 (t, 3H, J=7.2 Hz). LRMS (ES)+: 436.4 (M+H)+.

Workup

  1. temperaturewas cooled
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC (
  8. washC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and the product
  9. additioncontaining fractions
  10. concentrationwere concentrated, free-based with aq ammonium hydroxide
  11. extractionextracted with chloroform
  12. washwashed with brine
  13. dry with materialdried (K2CO3)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-820bfe7f398d4ebc8a85809d889d21a2
Source dataset
uspto-grants-2004_03
Patent number
US06699852B2

Linked notes

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