Triethylamine → 2-(7-Chloro-1,8-naphthyridin-2-yl)-3-methoxycarbonylmethylaminocarbonyloxy-isoindolin-1-one

HRID 66341Notes

Reaction equation

HRID 66341 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH:20]([OH:21])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:22])=[N:9]2)=[CH:4][CH:3]=1.[N:23]([CH2:26][C:27]([O:29][CH3:30])=[O:28])=[C:24]=[O:25].C(N(CC)CC)C>C(#N)C>[Cl:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH:20]([O:21][C:24]([NH:23][CH2:26][C:27]([O:29][CH3:30])=[O:28])=[O:25])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:22])=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2769479Methyl 2-isocyanatoacetate2×HCID 199004082-(7-Chloro-1,8-naphthyridin-2-yl)-3-hydroxyisoindolin-1-one

Product 1

HCID 227547422-(7-Chloro-1,8-naphthyridin-2-yl)-3-methoxycarbonylmethylaminocarbonyloxy-isoindolin-1-oneYield 57.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

A suspension of 2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one (3.2 g.), methyl 2-isocyanatoacetate (1.4 g.) and triethylamine (1.2 g.) in acetonitrile (50 cc.) is stirred for 18 hours at a temperature of about 20° C. A further amount of methyl 2-isocyanatoacetate (0.7 g.) is added and stirring is continued for a further 3 hours. The precipitate is filtered off and is dissolved in methylene chloride (35 cc.). Decolourising charcoal (0.5 g.) is added. After filtration, diisopropyl ether (105 cc.) is added to the filtrate. The crystalline precipitate which forms is filtered off, washed with diisopropyl ether (15 cc.) and then dried to give 2-(7-chloro-1,8-naphthyridin-2-yl)-3-methoxycarbonylmethylaminocarbonyloxy-isoindolin-1-one (2.5 g.) melting at 208°-210° C.

Workup

  1. stirringstirring
  2. waitis continued for a further 3 hours
  3. filtrationThe precipitate is filtered off
  4. dissolutionis dissolved in methylene chloride (35 cc.)
  5. additionDecolourising charcoal (0.5 g.) is added
  6. filtrationAfter filtration, diisopropyl ether (105 cc.)
  7. additionis added to the filtrate
  8. filtrationThe crystalline precipitate which forms is filtered off
  9. washwashed with diisopropyl ether (15 cc.)
  10. customdried

Sources & evidence

ORD record
ord-ee80e857e132454f926ed910dfa83ab2
Source dataset
uspto-grants-1978_12
Patent number
US04131674

Reaction notes

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