Reaktion #659295

Reaktionsgleichung

Intermediate 1d

(1R,4S)-4-Amino-1,2,3,4-tetrahydro-naphthalen-1-ol

sodium hydride

Intermediate 34b

3-Cyclohexyl-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

→

(1S,4R)-4-(3-Cyclohexyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe cooled solution was concentrated in vacuo
2. 2
   workup.DISSOLUTIONredissolved in MeOH (2 mL)
3. 3
   Waschenwashed with MeOH
4. 4
   WaschenThe product was eluted with 2M NH3 in MeOH
5. 5
   Einengenconcentration in vacuo
6. 6
   workup.WAITleft a brown oil
7. 7
   SonstigeFlash chromatography (silica 25 g, 2-10% [2M NH3 in MeOH] in DCM) gave a yellow oil
8. 8
   TrocknenFreeze-drying from MeCN-water (1:2, 3 mL)
9. 9
   workup.WAITleft the title compound as a pale yellow solid (203 mg, 56%)

Vorschrift

An opaque brown solution of Intermediate 1d (171 mg, 1.05 mmol) and sodium hydride (60% dispersion in oil, 120 mg, 3.00 mmol) in dry DMF (2 mL) was stirred at RT under Argon for 30 min. Intermediate 34b (219 mg, 1.00 mmol) was added, and the resulting dark solution stirred at 60° C. for 2 h. The cooled solution was concentrated in vacuo, redissolved in MeOH (2 mL), applied to an SCX-2 cartridge, and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo left a brown oil. Flash chromatography (silica 25 g, 2-10% [2M NH3 in MeOH] in DCM) gave a yellow oil. Freeze-drying from MeCN-water (1:2, 3 mL) left the title compound as a pale yellow solid (203 mg, 56%). LCMS (Method 3): Rt 2.29 min, m/z 363 [MH+].

Quelle