Triethylamine → (4R)-3-Fluoro-4-({4-[([1,2,3]thiadiazolo[5,4-b]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Dihydrochloride

HRID 15370

Reaktionsgleichung

Reaktionsgleichung von HRID 15370
[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[C:7]([CH2:10]O)[CH:8]=2)[S:3][N:2]=1.C(N(CC)CC)C.CS([Cl:23])(=O)=O.[NH2:24][CH:25]1[CH2:30][CH2:29][N:28]([CH2:31][C@H:32]2[C:36]3=[C:37]([F:45])[CH:38]=[N:39][C:40]4[CH:41]=[CH:42][C:43](=[O:44])[N:34]([C:35]=43)[CH2:33]2)[CH2:27][CH2:26]1.C(OC(=O)NC1CCNCC1O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.CO.ClCCl.CN(C=O)C>[ClH:23].[ClH:23].[F:45][C:37]1[CH:38]=[N:39][C:40]2[CH:41]=[CH:42][C:43](=[O:44])[N:34]3[CH2:33][C@@H:32]([CH2:31][N:28]4[CH2:27][CH2:26][CH:25]([NH:24][CH2:10][C:7]5[CH:8]=[C:9]6[N:1]=[N:2][S:3][C:4]6=[N:5][CH:6]=5)[CH2:30][CH2:29]4)[C:36]=1[C:35]=23

Komponenten

11

Edukt 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 21873601[1,2,3]Thiadiazolo[5,4-b]pyridin-6-ylmethanolHCID 57525698trans-4-(Boc-amino)-3-hydroxypiperidineHCID 68686964(4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

Produkt 1

HCID 68686862(4R)-3-Fluoro-4-({4-[([1,2,3]thiadiazolo[5,4-b]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one DihydrochlorideAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of [1,2,3]thiadiazolo[5,4-b]pyridin-6-ylmethanol (for a synthesis see WO2003064431, Example 1(b(iv)) (28 mg, 0.166 mmol) in THF (1 ml) was added triethylamine (0.023 ml, 0.166 mmol) and then methanesulfonyl chloride (0.013 ml, 0.166 mmol) and the reaction was then stirred at room temperature for 2 h. DMF (1 ml) was then added followed by (4R)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Enantiomer 1 (50 mg, 0.166 mmol) and potassium carbonate (0.166 mmol) and the reaction was stirred at room temperature for a further 72 h before evaporation. The residue was subjected to column chromatography on silica gel using a dichloromethane, methanol gradient to provide the free base of the title compound (20 mg, 27%).

Quellen und Nachweise

ORD-Eintrag
ord-4282adf516d74e11b7fada8af21fe8a7
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732461B2

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