1,2-Dichloroethane → 3-(1,3-dioxoisoindolin-2-yl)-N-(isoquinolin-6-yl)-2-(4-((triisopropylsilyloxy)methyl)phenyl)propanamide

HRID 1020095Notes

Reaction equation

HRID 1020095 reaction equation
[C:1]([CH:4]([C:18]1[CH:23]=[CH:22][C:21]([CH2:24][O:25][Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])=[CH:20][CH:19]=1)[CH2:5][NH:6][C:7]([C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1[C:11](O)=[O:12])=[O:8])([OH:3])=O.C(Cl)CCl.[NH2:40][C:41]1[CH:42]=[C:43]2[C:48](=[CH:49][CH:50]=1)[CH:47]=[N:46][CH:45]=[CH:44]2>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[O:12]=[C:11]1[C:10]2[C:9](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:7](=[O:8])[N:6]1[CH2:5][CH:4]([C:18]1[CH:19]=[CH:20][C:21]([CH2:24][O:25][Si:26]([CH:33]([CH3:35])[CH3:34])([CH:27]([CH3:28])[CH3:29])[CH:30]([CH3:32])[CH3:31])=[CH:22][CH:23]=1)[C:1]([NH:40][C:41]1[CH:42]=[C:43]2[C:48](=[CH:49][CH:50]=1)[CH:47]=[N:46][CH:45]=[CH:44]2)=[O:3]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 5889916-AminoisoquinolineHCID 595638082-(2-Carboxy-2-(4-((triisopropylsilyloxy)methyl)phenyl)ethylcarbamoyl)benzoic acid

Product 1

HCID 595636953-(1,3-dioxoisoindolin-2-yl)-N-(isoquinolin-6-yl)-2-(4-((triisopropylsilyloxy)methyl)phenyl)propanamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

To 2-(2-carboxy-2-(4-((triisopropylsilyloxy)methyl)phenyl)ethylcarbamoyl)benzoic acid (E135) in pyridine was added EDC, DMAP and 6-aminoisoquinoline and the solution was flushed with N2, capped, and stirred overnight. The mixture was poured into EtOAc/NaHCO3(sat) and the aqueous layer was further extracted with EtOAc. The organics were dried (MgSO4), filtered, and evaporated. Column chromatography (SiO2, 5% MeOH/CH2Cl2) gave pure 3-(1,3-dioxoisoindolin-2-yl)-N-(isoquinolin-6-yl)-2-(4-((triisopropylsilyloxy)methyl)phenyl)propanamide (E136).

Workup

  1. customthe solution was flushed with N2
  2. customcapped
  3. additionThe mixture was poured into EtOAc/NaHCO3(sat)
  4. extractionthe aqueous layer was further extracted with EtOAc
  5. dry with materialThe organics were dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-7fead24ba99e403fb1673799e66f96c4
Source dataset
uspto-grants-2014_05
Patent number
US08716310B2

Reaction notes

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