Sodium hydride → (1S,4R)-4-[3-((S)-3-Methyl-morpholin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

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Reaktionsgleichung

[H-].[Na+].[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([OH:14])[CH2:6][CH2:5]1.F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][C@@H:26]3[CH3:31])=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH3:31][C@H:26]1[CH2:27][O:28][CH2:29][CH2:30][N:25]1[C:22]1[N:20]2[CH:21]=[C:16]([O:14][C@H:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C@@H:4]([NH2:3])[CH2:5][CH2:6]3)[CH:17]=[CH:18][C:19]2=[N:24][N:23]=1

Komponenten

Reaktionsbedingungen

Temperatur: 60 °C

Versuchsvorschrift

To a suspension of sodium hydride (60% in mineral oil, 187 mg, 4.68 mmol) in DMF (6.0 mL) was added Intermediate A (191 mg, 1.17 mmol) and the reaction stirred for 20 min. Intermediate 139b (276 mg, 1.17 mmol) was added in DMF (2.00 mL) and the reaction heated to 60° C. for 1 h. The reaction was cooled and quenched by dropwise addition of methanol, before being diluted with methanol and loaded onto an SCX-2 cartridge, which was washed with MeOH. The product was eluted with 2M NH3 in MeOH. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (250 mg, 56%). LCMS (Method 4): Rt 1.83, m/z 380 [MH+].

Aufarbeitung

temperatureThe reaction was cooled
customquenched by dropwise addition of methanol
additionbefore being diluted with methanol
washwas washed with MeOH
washThe product was eluted with 2M NH3 in MeOH
customThe residue was purified by FCC

Quellen und Nachweise

ORD-Eintrag: ord-4b567fb86d5e410bb3291c560db8558a
Quelldatensatz: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09315503B2

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