반응 #1133127

반응 방정식

9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene

8-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one

8-[(2,5-dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one

1-Methylpyrazol-5-amine

cesium carbonate

→

8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one

수율 69.9%

용매

dioxane

반응 조건

후처리

1. 1
   기타sealed in a tube
2. 2
   기타The reaction was degased
3. 3
   기타purged with nitrogen
4. 4
   여과The reaction mixture was filtered
5. 5
   세척washed with DCM
6. 6
   농축concentrated to dryness
7. 7
   기타The reaction mixture was purified by preparative HPLC
8. 8
   기타The fractions were evaporated to dryness

실험 절차

8-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one (100 mg, 0.31 mmol, example 3.23), 1-Methylpyrazol-5-amine (60.3 mg, 0.62 mmol), cesium carbonate (121 mg, 0.37 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (28.7 mg, 0.05 mmol) and palladium(II) acetate (5.57 mg, 0.02 mmol) were suspended in dioxane (2 mL) and sealed in a tube. The reaction was degased, purged with nitrogen and heated to 100° C. for 12 hours. The reaction mixture was filtered, washed with DCM and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (83 mg, 69.8%) as a grey solid. 1H NMR spectrum (500 MHz, DMSO): 2.95 (t, 2H), 3.05 (s, 3H), 3.56 (t, 2H), 3.63 (s, 3H), 6.19 (d, 1H), 6.86 (s, 1H), 6.91 (dd, 1H), 7.29 (d, 1H), 7.42 (s, 1H), 7.43 (d, 1H), 8.02 (s, 1H), 8.68 (s, 1H), 11.26 (s, 1H); Mass spectrum: ESI+ MH+ 383.

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