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Acetic Acid → (R)-2-(4-Chloro-2-methoxypyridin-3-yl)-6-(2,3-dihydroxypropyl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione

HRID 920490
Notes
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Reaction equation

HRID 920490 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[N+:11]([O-])=O)[C:7](=[O:14])[N:6]([CH2:15][C@@H:16]([OH:19])[CH2:17][OH:18])[C:5]2=[O:20].CC(O)=O.[H][H].[Cl:27][C:28]1[C:33]([CH:34]=O)=[C:32]([O:36][CH3:37])[N:31]=[CH:30][CH:29]=1>CO.[Pd]>[Cl:27][C:28]1[CH:29]=[CH:30][N:31]=[C:32]([O:36][CH3:37])[C:33]=1[C:34]1[NH:11][C:10]2=[CH:9][C:8]3[C:7](=[O:14])[N:6]([CH2:15][C@@H:16]([OH:19])[CH2:17][OH:18])[C:5](=[O:20])[C:4]=3[CH:3]=[C:2]2[N:1]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 534079284-Chloro-2-methoxypyridine-3-carbaldehydeHCID 66686469(R)-5-Amino-2-(2,3-dihydroxypropyl)-6-nitroisoindoline-1,3-dioneHCID 178418361HCID 178418361, compound

Product 1

HCID 66687275(R)-2-(4-Chloro-2-methoxypyridin-3-yl)-6-(2,3-dihydroxypropyl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione
Yield 29.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Conditions

Temperature
-30 °C

Procedure

To a suspension of (R)-5-amino-2-(2,3-dihydroxypropyl)-6-nitroisoindoline-1,3-dione (0.50 g, 1.78 mmol) in 100 mL of MeOH was added 5 mL of AcOH. The resulting solution was degassed with Argon and then charged with 10% Pd/C (0.19 g, 50% wet, 0.089 mmol) and hydrogenated at 40 psi of hydrogen for 16 h. Another 5 mL of AcOH was added to the mixture and then solids were filtered off. The filtrate was cooled to −30° C. and a solution of 4-chloro-2-methoxynicotinaldehyde (0.31 g, 1.78 mmol) in 50 mL of MeOH was added dropwise under inert atmosphere. The resulting red clear solution was allowed to warm up to rt and stirred for 16 h. Solvent was evaporated and the oily residue was purified by column chromatography (7.5% MeOH in dichloromethane) to give title compound as a yellow solid (0.21 g, 29.3%). 1H NMR (500 MHz, DMSO-d6) δ58.37 (d, J=5.5 Hz, 1H), 8.07 (s, 2H), 7.40 (d, J=5.5 Hz, 1H), 4.92 (d, J=5.0 Hz, 1H), 4.67 (br s, 1H), 4.20-4.14 (br s, 1H), 3.90 (s, 3H), 3.90-3.80 (m, 1H), 3.64-3.60 (m, 2H), 3.42-3.36 (m, 2H). ESI MS: m/z 403.1 (M+1).

Workup

  1. customThe resulting solution was degassed with Argon
  2. filtrationsolids were filtered off
  3. temperatureto warm up to rt
  4. customSolvent was evaporated
  5. customthe oily residue was purified by column chromatography (7.5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-4065f08fbd5f4951b1669f3d5c50d613
Source dataset
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09273055B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes