Toluene → tert-butyl (1'-benzyl-1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methylcarbamate

Participants

Reaction Conditions

Reaction Steps

A 3-neck round bottom flask was charged with tert-butyl (1′-benzylspiro[indoline-3,4′-piperidine]-4-yl)methylcarbamate (446 mg, 1.09 mmol; see Example 27, Step 3), Pd(OAc)2 (24.6 mg, 0.109 mmol), Xantphos (95 mg, 0.164 mmol) and Cs2CO3 (536 mg, 1.64 mmol) and purged with N2. Toluene (6 mL, 0.547 mmol; sparged with N2 for 30 minutes) and 4-chloro-5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (200 mg, 1.09 mmol) were injected into the reaction, and the reaction was heated to 95° C. for 24 hours. LCMS showed most of the starting material had been consumed. The reaction was cooled, mixed with EtOAc and filtered through glass filter paper. The filtrate was concentrated to a residue and purified by silica gel chromatography (gradient: 5-50% (80 DCM: 19 MeOH: 1 NH4OH)/DCM). Purification provided tert-butyl (1′-benzyl-1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methylcarbamate (422 mg, 0.762 mmol, 70% yield). 1H NMR (CDCl3, 400 MHz) δ 8.62 (s, 1H), 7.29-7.35 (m, 5H), 7.25 (m, 1H), 7.16 (t, 1H), 6.91 (d, 1H), 4.54 (br.s, 1H), 4.20-4.30 (m, 3H), 3.97 (m, 2H), 3.53 (s, 2H), 3.27 (m, 1H), 2.85-2.97 (m, 4H), 2.51 (m, 1H), 2.26 (m, 1H), 2.11 (d, 2H), 2.04 (t, 1H), 1.85 (m, 1H), 1.75 (d, 1H), 1.59 (d, 1H), 1.46 (s, 9H), 1.18 (m, 1H), 0.77 (t, 3H). MS (APCI+) [M+H]: 554.2.

Provenance & Evidence