Triethylamine → 2-(7-Chloro-5-methyl-1,8-naphthyridin-2-yl)-3-[2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-oxoethyl]-2,3-dihydro-1H-isoindol-1-one

HRID 868253Notes

Reaction equation

HRID 868253 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.P(C#N)(=O)(OCC)OCC.[Cl:28][C:29]1[N:38]=[C:37]2[C:32]([CH:33]=[CH:34][C:35]([N:39]3[C:47](=[O:48])[C:46]4[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=4)[CH:40]3[CH2:49][C:50](O)=[O:51])=[N:36]2)=[C:31]([CH3:53])[CH:30]=1>CN(C)C=O>[Cl:28][C:29]1[N:38]=[C:37]2[C:32]([CH:33]=[CH:34][C:35]([N:39]3[CH:40]([CH2:49][C:50]([N:8]4[CH2:9][CH2:10][C:5]5([O:4][CH2:3][CH2:2][O:1]5)[CH2:6][CH2:7]4)=[O:51])[C:41]4[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=4)[C:47]3=[O:48])=[N:36]2)=[C:31]([CH3:53])[CH:30]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 76257Diethyl cyanophosphonateHCID 212880692-(7-Chloro-5-methyl-1,8-naphthyridin-2-yl)-3-oxoisoindoline-1-acetic acid

Product 1

HCID 136559462-(7-Chloro-5-methyl-1,8-naphthyridin-2-yl)-3-[2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-oxoethyl]-2,3-dihydro-1H-isoindol-1-oneYield 90.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

With ice-cooling and stirring, 1.6 g of 1,4-dioxa-8-azaspiro[4.5]decane, 2 ml of triethylamine and 2.2 g of diethyl phosphorocyanidate were successively added to a solution of 3.5 g of 2-(7-chloro-5-methyl-1,8-naphthyridin-2-yl)-3-oxoisoindoline-1-acetic acid in 30 ml of dimethylformamide. The mixture was stirred with ice-cooling for an additional 2 hours and 200 ml of ice-water was added thereto. The mixture was allowed to stand, and the resulting crystalline precipitate was collected by filtration, washed with water and dried. Recrystallization from dichloromethane-ether (1:4) gave 4.23 g of colorless crystals melting at 259°-262° C.

Workup

  1. temperatureWith ice-cooling
  2. stirringThe mixture was stirred with ice-
  3. temperaturecooling for an additional 2 hours
  4. filtrationthe resulting crystalline precipitate was collected by filtration
  5. washwashed with water
  6. customdried
  7. customRecrystallization from dichloromethane-ether (1:4)

Sources & evidence

ORD record
ord-c1b4e6e3fe7a4e8da5fecc9c2b13117c
Source dataset
uspto-grants-1988_10
Patent number
US04778801

Reaction notes

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