Triphenylphosphine → methyl 2-bromo-7-(2-morpholinoethoxy)-5H-pyrido[3,2-b]indole-4-carboxylate

HRID 2410767Notes

Reaction equation

HRID 2410767 reaction equation
N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:32][C:33]1[CH:34]=[C:35]([C:47]([O:49][CH3:50])=[O:48])[C:36]2[NH:37][C:38]3[CH:39]=[C:40]([OH:46])[CH:41]=[CH:42][C:43]=3[C:44]=2[N:45]=1.[O:51]1[CH2:56][CH2:55][N:54]([CH2:57][CH2:58]O)[CH2:53][CH2:52]1>C1COCC1>[Br:32][C:33]1[CH:34]=[C:35]([C:47]([O:49][CH3:50])=[O:48])[C:36]2[NH:37][C:38]3[CH:39]=[C:40]([O:46][CH2:58][CH2:57][N:54]4[CH2:55][CH2:56][O:51][CH2:52][CH2:53]4)[CH:41]=[CH:42][C:43]=3[C:44]=2[N:45]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 178497039HCID 178497039, compound

Product 1

HCID 86663030methyl 2-bromo-7-(2-morpholinoethoxy)-5H-pyrido[3,2-b]indole-4-carboxylateYield 53.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (790 μL, 5.0 mmol) was added to a solution of triphenylphosphine (1.31 g, 5.0 mmol), methyl 2-bromo-7-hydroxy-5H-pyrido[3,2-b]indole-4-carboxylate (800 mg, 2.49 mmol) and 2-morpholinoethanol (610 μL, 5.0 mmol) in dry THF (12 mL) at room temperature under nitrogen. After 1 hr, the reaction was partitioned between EtOAc and water and the organic phase was washed with brine and dried over sodium sulfate. The solvent was removed and the residue was taken up in a 1:1 mixture of DCM:MeOH and the product was captured on a SCX cartridge and released with a 1:1 mixture of 2 N NH3 in MeOH:DCM. The solvent was removed and the product was purified by radial chromatography (step gradient elution with DCM containing 0 to 3% MeOH) to afford methyl 2-bromo-7-(2-morpholinoethoxy)-5H-pyrido[3,2-b]indole-4-carboxylate (577 mg, 1.33 mmol, 53% yield) as a tan solid. MS (ESI) m/z 434.0 (M+H). 1H NMR (400 MHz, chloroform-d) δ ppm 9.48 (1H, s), 8.21 (1H, d, J=9.32 Hz), 7.88 (1H, s), 6.89-7.00 (2H, m), 4.22 (2H, t, J=5.67 Hz), 4.04 (3H, s), 3.70-3.80 (3H, m), 3.69-3.81 (4H, m), 2.86 (2H, t, J=5.67 Hz), 2.55-2.65 (4H, m).

Workup

  1. customthe reaction was partitioned between EtOAc and water
  2. washthe organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed
  5. additionthe residue was taken up in a 1:1 mixture of DCM
  6. additionreleased with a 1:1 mixture of 2 N NH3 in MeOH
  7. customThe solvent was removed
  8. customthe product was purified by radial chromatography (step gradient elution with DCM containing 0 to 3% MeOH)

Sources & evidence

ORD record
ord-7bf84e9455f14562863cec3bf78f1101
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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