Phosphorus oxychloride → 2-(7-Chloro-1,8-naphthyridin-2-yl)-5-chloro-3-hydroxy-isoindolin-1-one

HRID 259651

반응식

HRID 259651 반응식
[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(OC4C=CC=CC=4)=O)[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([Cl:31])[CH:18]=4)[C:13]3=[O:32])=[N:9]2)=[CH:4][CH:3]=1.ClC1C=C2C(=O)OC(=O)C2=CC=1.NC1C=CC2C(=NC(O)=CC=2)N=1.OC1N=C2C(C=CC(C34C=CC(Cl)=CC3C(NC4=O)=O)=N2)=CC=1.ClC1N=C2C(C=CC(C34C=CC(Cl)=CC3C(NC4=O)=O)=N2)=CC=1.P(Cl)(Cl)(Cl)=O.[BH4-].[K+].ClC1N=C2C(C=CC(N3C(O)C4C(=CC(Cl)=CC=4)C3=O)=N2)=CC=1>C(O)(=O)C.CO.O1CCOCC1.CN(C)C=O>[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]=[C:17]([Cl:31])[CH:18]=4)[C:13]3=[O:32])=[N:9]2)=[CH:4][CH:3]=1

참가 물질

13

반응물 8

HCID 24813Phosphorus oxychlorideHCID 670444-Chlorophthalic anhydride2회HCID 4192641Potassium borohydrideHCID 198422416-Chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinoneHCID 214221182-(7-Chloro-1,8-naphthyridin-2-yl)-3-phenoxycarbonyloxy-5-chloro-isoindolin-1-oneHCID 227547452-(7-Chloro-1,8-naphthyridin-2-yl)-5-chlorophthalimide2회HCID 178507296HCID 178507296, 화합물2회HCID 178518247HCID 178518247, 화합물2회

생성물 1

HCID 198422422-(7-Chloro-1,8-naphthyridin-2-yl)-5-chloro-3-hydroxy-isoindolin-1-one

시약·촉매·용매 4

HCID 176Acetic Acid용매HCID 887Methanol용매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

실험 절차

2-(7-Chloro-1,8-naphthyridin-2-yl)-3-phenoxycarbonyloxy-5-chloro-isoindolin-1-one can be prepared in the following way: Preparation of 4-chlorophthalic anhydride, m.p. 96° C., according to E. E. Ayling, J. Chem. Soc., 1929, 253. Preparation of 2-amino-7-hydroxy-1,8-naphthyridine, m.p. 300°-305° C., according to S. Carboni et al, Ann. Chim. (Roma), 54, 883 (1964). Preparation of 2-(7-hydroxy-1,8-naphthyridin-2-yl)-5-chlorophthalimide (7 g.), m.p. 320° C., by reacting 2-amino-7-hydroxy-1,8-naphthyridine (9.5 g.) with 4-chlorophthalic anhydride (21.5 g.) in acetic acid (450 cc.) for 1 hour at 116° C. Preparation of 2-(7-chloro-1,8-naphthyridin-2-yl)-5-chlorophthalimide (6.4 g.), m.p. 280° C., by reacting phosphorus oxychloride (70 cc.) with 2-(7-hydroxy-1,8-naphthyridin-2-yl)-5-chlorophthalimide (7 g.) in the presence of dimethylformamide (0.7 cc.). By reacting potassium borohydride (0.75 g.) with 2-(7-chloro-1,8-naphthyridin-2-yl)-5-chlorophthalimide (6.4 g.) in a mixture (300 cc.) of dioxan and methanol (50--50 by volume), a mixture (5.2 g.) of 2-(7-chloro-1,8-naphthyridin-2-yl)-5-chloro-3-hydroxy-isoindolin-1-one and 2-(7-chloro-1,8-naphthyridin-2-yl)-6-chloro-3-hydroxy-isoindolin-1-one is obtained. This mixture is recrystallised firstly from dichloroethane (700 cc.) and then a second time from the same solvent (315 cc.). A product (1.51 g.) is thus obtained and is recrystallised successively from bromoform (38 cc.) and then from a mixture (104.5 cc.) of dichloroethane and ethanol (91-9 by volume). 2-(7-Chloro-1,8-naphthyridin-2-yl)-5-chloro-3-hydroxy-isoindolin-1-one (0.65 g.) is thus obtained. Preparation of 2-(7-chloro-1,8-naphthyridin-2-yl)-5-chloro-3-phenoxycarbonyloxy-isoindolin-1-one (1.6 g.), m.p. 220°-230° C., from 2-(7-chloro-1,8-naphthyridin-2-yl)-5-chloro-3-hydroxy-isoindolin-1-one (1 g.) and phenyl chloroformate (1.36 g.) in anhydrous pyridine (15 cc.).

후처리

  1. customfor 1 hour
  2. customat 116° C

출처 및 근거

ORD 기록
ord-8b160674f4734597880aaf0532cf6a54
출처 데이터셋
uspto-grants-1977_07
특허 번호
US04038391

연결된 노트

불러오는 중…