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Phthaloyl chloride → (S)-3-[1-(1,3-dioxo-1,3-dihydroisoindol-2-yl)isoquinolin-6-yloxy]piperidine-1-carboxylic acid tert-butyl ester

HRID 1435970
Notes
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Reaction equation

HRID 1435970 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[C:21]([NH2:25])=[N:20][CH:19]=[CH:18]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:33](Cl)(=[O:43])[C:34]1[C:35](=[CH:39][CH:40]=[CH:41][CH:42]=1)[C:36](Cl)=[O:37]>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[C:21]([N:25]2[C:36](=[O:37])[C:35]4[C:34](=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:33]2=[O:43])=[N:20][CH:19]=[CH:18]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 6955Phthaloyl chlorideHCID 8471TriethylamineHCID 68875514(S)-3-(1-amino-isoquinolin-6-yloxy)piperidin-1-carboxylic acid tert-butyl ester

Product 1

HCID 68874394(S)-3-[1-(1,3-dioxo-1,3-dihydroisoindol-2-yl)isoquinolin-6-yloxy]piperidine-1-carboxylic acid tert-butyl esterYield 74.2%

Reagents, catalysts & solvents 1

HCID 962
Water
Solvent

Procedure

To a solution of (S)-3-(1-amino-isoquinolin-6-yloxy)piperidin-1-carboxylic acid tert-butyl ester (380 mg, 1.11 mmol) and triethylamine (1.5 ml, 11.1 mmol) in anhydrous tetraydrofuran (1.5 ml) was added phthaloyl dichloride (170 μL, 1.16 mmol). The mixture was stirred at ambient temperature for 2 h and then poured into quickly stirring water. The mixture was extracted with dichloromethane (3×50 ml) and concentrated in vacuo to give a residue. Flash chromatography of the residue on silica (eluent: 0-100% ethyl acetate in heptane) gave (S)-3-[1-(1,3-dioxo-1,3-dihydroisoindol-2-yl)isoquinolin-6-yloxy]piperidine-1-carboxylic acid tert-butyl ester (390 mg) E1l-MS: m/z=474.3 [M+H]+.

Workup

  1. extractionThe mixture was extracted with dichloromethane (3×50 ml)
  2. concentrationconcentrated in vacuo
  3. customto give a residue

Sources & evidence

ORD record
ord-4722e7cd784f4e37bac0dee730fa5e1d
Source dataset
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07618985B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes