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Diisopropylethylamine → 2-(((2S,3R)-3-Methyl-1-(5-methyl-2-(pyridazin-3-yl)benzoyl)piperidin-2-yl)methyl)isoindoline-1,3-dione

HRID 61127
Notes
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Reaction equation

HRID 61127 reaction equation
[CH3:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][NH:4][C@@H:3]1[CH2:8][N:9]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]1=[O:19].[CH3:20][C:21]1[CH:22]=[CH:23][C:24]([C:30]2[N:31]=[N:32][CH:33]=[CH:34][CH:35]=2)=[C:25]([CH:29]=1)[C:26](O)=[O:27].CCN(C(C)C)C(C)C.CCCP(=O)=O>C(Cl)Cl>[CH3:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:26](=[O:27])[C:25]2[CH:29]=[C:21]([CH3:20])[CH:22]=[CH:23][C:24]=2[C:30]2[N:31]=[N:32][CH:33]=[CH:34][CH:35]=2)[C@@H:3]1[CH2:8][N:9]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]1=[O:19]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 1177276302-(((2S,3R)-3-Methylpiperidin-2-yl)methyl)isoindoline-1,3-dioneHCID 1177277195-Methyl-2-(pyridazin-3-yl)benzoic acid

Product 1

HCID 1177276722-(((2S,3R)-3-Methyl-1-(5-methyl-2-(pyridazin-3-yl)benzoyl)piperidin-2-yl)methyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a mixture of 2-(((2S,3R)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione (1.09 g, 4.20 mmol), 5-methyl-2-(pyridazin-3-yl)benzoic acid (0.75 g, 3.5 mmol) and DIPEA (1.8 mL, 10.5 mmol) in DCM (20 mL) was added propylphosphonic anhydride (T3P) (50% in EtOAc, 4.2 mL, 7.0 mmol). The mixture was heated at 40° C. for 16 h. The mixture was cooled to rt and diluted with DCM. The mixture was washed with satd. aq. NaHCO3, brine, and dried (MgSO4). The solvent was removed in vacuo. The crude was purified by chromatography on silica gel (EtOAc/hexanes) to afford the title compound. ESI-MS (m/z): 455 [M+1]+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. washThe mixture was washed with satd
  3. dry with materialaq. NaHCO3, brine, and dried (MgSO4)
  4. customThe solvent was removed in vacuo
  5. customThe crude was purified by chromatography on silica gel (EtOAc/hexanes)

Sources & evidence

ORD record
ord-8840b7f974ce4a5783a9ea189d8f630b
Source dataset
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09440982B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes