(4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one → Isopropylamine

HRID 15166

Reaktionsgleichung

Reaktionsgleichung von HRID 15166
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@@:9]2([OH:24])[C:13]3=[C:14]([F:23])[CH:15]=[N:16][C:17]4[CH:18]=[C:19]([F:22])[C:20](=[O:21])[N:11]([C:12]=43)[CH2:10]2)[CH2:4][CH2:3]1.[NH2:25][CH:26]1[CH2:31][CH2:30][N:29]([CH2:32][C@:33]2([OH:47])[C:37]3=[C:38]([F:46])[CH:39]=[N:40][C:41]4[CH:42]=[CH:43][C:44](=[O:45])[N:35]([C:36]=43)[CH2:34]2)[CH2:28][CH2:27]1>>[CH:2]([NH2:1])([CH3:7])[CH3:3].[NH2:1][CH:2]1[CH2:3][CH2:4][N:5]([CH2:8][C@@:9]2([OH:24])[C:13]3=[C:14]([F:23])[CH:15]=[N:16][C:17]4[CH:18]=[C:19]([F:22])[C:20](=[O:21])[N:11]([C:12]=43)[CH2:10]2)[CH2:6][CH2:7]1.[NH2:25][CH:26]1[CH2:27][CH2:28][N:29]([CH2:32][C@:33]2([OH:47])[C:37]3=[C:38]([F:46])[CH:39]=[N:40][C:41]4[CH:42]=[CH:43][C:44](=[O:45])[N:35]([C:36]=43)[CH2:34]2)[CH2:30][CH2:31]1

Komponenten

5

Edukt 2

HCID 23633344(4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneHCID 23633410(4S)-4-[(4-amino-1-piperidinyl)methyl]-3,8-difluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

Produkt 3

HCID 6363IsopropylamineHCID 23633344(4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneHCID 23633410(4S)-4-[(4-amino-1-piperidinyl)methyl]-3,8-difluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

Versuchsvorschrift

(4R/S)-4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3,4-difluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-1-one (43 mg) was resolved by preparative chiral HPLC into the two enantiomers E1 and E2 using a Chiralpak AD-H column, eluting with 50:50:0.1 acetonitrile:methanol:isopropylamine, affording enantiomers E1 (first eluting) and E2 (second eluting) which were converted to the mono hydrochloride salts by dissolving in methanol, adding 1 equivalent of aqueous 6.0N HCl and evaporating to dryness.

Aufarbeitung

  1. washeluting with 50:50:0.1 acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-4082a28ab5ba4005a212004508e091d1
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732460B2

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