Acetic Acid → HCID 86663039, compound

HRID 2410786Notes

Reaction equation

HRID 2410786 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH:15]=O)=[CH:11][C:12]=3[C:13]=2[N:14]=1.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CN(C=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH2:15][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[CH:11][C:12]=3[C:13]=2[N:14]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 86663038HCID 86663038, compound

Product 1

HCID 86663039HCID 86663039, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of methyl 2-bromo-8-formyl-5H-pyrido[3,2-b]indole-4-carboxylate (200 mg, 0.600 mmol) in DMF (1 mL) was stirred for 5 min and then diluted with DCM (10 mL). Morpholine (0.063 mL, 0.720 mmol) was added and the suspension was cooled in an ice bath. Sodium triacetoxyborohydride (344 mg, 1.62 mmol) was added and the suspension was left stirring for 0.5 hr. Acetic acid (0.069 mL, 1.20 mmol) was then added and the bath removed. The reaction was left stirring at RT overnight. It was diluted with DCM and washed with sat. aq. NaHCO3 solution followed by water (2×). After drying with sodium sulfate, the solvent was removed and radial chromatography (step gradient elution with DCM containing 0 to 3% MeOH) afforded methyl 2-bromo-8-(morpholinomethyl)-5H-pyrido[3,2-b]indole-4-carboxylate (143 mg, 0.354 mmol, 59% yield) as dark green solid. MS (ESI) m/z 436.10 (M+H). 1H NMR (400 MHz, chloroform-d) δ ppm 9.55 (1H, br. s.), 8.27 (1H, s), 7.94 (1H, s), 7.56 (1H, dd, J=8.31, 1.51 Hz), 7.45 (1H, d, J=8.31 Hz), 4.04 (3H, s), 3.66-3.74 (4H, m), 3.64 (2H, s), 2.46 (4H, br. s.).

Workup

  1. temperaturethe suspension was cooled in an ice bath
  2. waitthe suspension was left
  3. stirringstirring for 0.5 hr
  4. customthe bath removed
  5. waitThe reaction was left
  6. stirringstirring at RT overnight
  7. additionIt was diluted with DCM
  8. washwashed with sat. aq. NaHCO3 solution
  9. dry with materialAfter drying with sodium sulfate
  10. customthe solvent was removed
  11. washradial chromatography (step gradient elution with DCM containing 0 to 3% MeOH)

Sources & evidence

ORD record
ord-fbfb392619bc49ffb9150f99adb65538
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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