2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b)[1,4]thiazepino[6,5,4-hi]indol-6-yl]-5-methoxybenzaldehyde → HCID 60071864, compound

HRID 47545Notes

Reaction equation

HRID 47545 reaction equation
[CH2:1]1[N:12]2[C:13]3[C:9]([C@@H:10]4[CH2:17][NH:16][CH2:15][CH2:14][C@@H:11]42)=[CH:8][C:7]([C:18]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:19]=2[CH:20]=[O:21])=[CH:6][C:5]=3[CH2:4][S:3][CH2:2]1.[CH3:28][Mg]Br>O1CCCC1>[CH2:1]1[N:12]2[C:13]3[C:9]([C@@H:10]4[CH2:17][NH:16][CH2:15][CH2:14][C@@H:11]42)=[CH:8][C:7]([C:18]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:19]=2[CH:20]([OH:21])[CH3:28])=[CH:6][C:5]=3[CH2:4][S:3][CH2:2]1

Participants

4

Reactant 2

HCID 206276552-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b)[1,4]thiazepino[6,5,4-hi]indol-6-yl]-5-methoxybenzaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 60071864HCID 60071864, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-[(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-6-yl]-5-methoxybenzaldehyde, the free base of EXAMPLE 16 (0.03 g, 0.08 mmol), in 5 mL of tetrahydrofuran at 0° C. was added methyl magnesium bromide (0.52 mL of a 3M solution in THF, 1.58 mmol). Stirred with warming to ambient temperature for several hours and then quenched with sat'd ammonium chloride. Extracted with ethyl acetate, washed organics with brine, dried (MgSO4) and concentrated. The residue was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA). Fractions containing desired compound were then immediately free based with 1 N sodium hydroxide, extracted with ethyl acetate, dried (MgSO4) and concentrated to afford the title compound of EXAMPLE 21. LRMS (ES+): 397.1 (M+H)+.

Workup

  1. customquenched with sat'd ammonium chloride
  2. extractionExtracted with ethyl acetate
  3. washwashed organics with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by prep HPLC (
  7. washC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA)
  8. additionFractions containing desired compound
  9. extractionextracted with ethyl acetate
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-26a9c631326541d393e542e6e305a58b
Source dataset
uspto-grants-2004_03
Patent number
US06699852B2

Reaction notes

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