Hydrochloric Acid → 2-((R)-3-(3,5-difluorophenyl)-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((S)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide

HRID 1615774Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1615774
[C:1]([CH2:4][N:5]1[C:10](=[O:11])[C:9]2([CH2:17][O:16][CH2:15][CH2:14][O:13][CH2:12]2)[N:8](C(OC(C)(C)C)=O)[CH2:7][C@H:6]1[C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[CH:26]=1)(O)=[O:2].[NH2:33][C:34]1[CH:35]=[C:36]2[C:49](=[CH:50][CH:51]=1)[CH2:48][C@@:38]1([C:46]3[C:41](=[N:42][CH:43]=[CH:44][CH:45]=3)[NH:40][C:39]1=[O:47])[CH2:37]2.Cl.C(N=C=NCCCN(C)C)C.C1C=CC2N(O)N=NC=2C=1.Cl>CN(C=O)C>[F:31][C:29]1[CH:30]=[C:25]([C@H:6]2[N:5]([CH2:4][C:1]([NH:33][C:34]3[CH:35]=[C:36]4[C:49](=[CH:50][CH:51]=3)[CH2:48][C@@:38]3([C:46]5[C:41](=[N:42][CH:43]=[CH:44][CH:45]=5)[NH:40][C:39]3=[O:47])[CH2:37]4)=[O:2])[C:10](=[O:11])[C:9]3([CH2:17][O:16][CH2:15][CH2:14][O:13][CH2:12]3)[NH:8][CH2:7]2)[CH:26]=[C:27]([F:32])[CH:28]=1

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54776259(S)-5-amino-1,3-dihydrospiro[indene-2,3-pyrrolo[2,3-b]pyridin]-2(1H)-oneHCID 68154191tert-butyl (R)-4-carboxymethyl-3-(3,5-difluoro-phenyl)-5-oxo-8,11-dioxa-1,4-diaza-spiro[5.6]dodecane-1-carboxylate

Produkt 1

HCID 498420252-((R)-3-(3,5-difluorophenyl)-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((S)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

0.114 g (0.25 mmol) tert-butyl (R)-4-carboxymethyl-3-(3,5-difluoro-phenyl)-5-oxo-8,11-dioxa-1,4-diaza-spiro[5.6]dodecane-1-carboxylate were stirred overnight at RT with 67.9 mg (0.27 mmol) (S)-5-amino-1,3-dihydrospiro[inden-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, 63.3 mg (0.33 mmol) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 44.6 mg (0.33 mmol) HOBT, 35 μl (0.25 mmol) TEA and 1.5 ml DMF. The solvent was spun off and the residue was stirred with 15 ml of a methanolic hydrochloric acid (1.25N) 1 h at 50° C. The reaction mixture was concentrated by rotary evaporation and the residue was purified by PR-HPLC. The product-containing fractions were concentrated by rotary evaporation and the residue was triturated with diisopropylether. After suction filtering the solid was washed with diisopropylether and dried.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated by rotary evaporation
  2. customthe residue was purified by PR-HPLC
  3. concentrationThe product-containing fractions were concentrated by rotary evaporation
  4. customthe residue was triturated with diisopropylether
  5. filtrationAfter suction filtering the solid
  6. washwas washed with diisopropylether
  7. customdried

Quellen und Nachweise

ORD-Eintrag
ord-bcf785bb42df4d11aa5407eac84b041c
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765763B2

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