반응 #2292796

반응 방정식

triethylamine

tert-butyl (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)piperazine-1-carboxylate

2,4-diamino-6-chloropyrimidine-5-carbonitrile

Triethylamine

→

title compound

수율 36.0%

tert-Butyl (S)-4-(5-(1-((2,6-diamino-5-cyanopyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)piperazine-1-carboxylate

수율 36.0%

용매

DMSO

반응 조건

후처리

1. 1
   기타to give a yellow suspension
2. 2
   workup.ADDITIONwas added
3. 3
   온도After a total of 4 hours of heating
4. 4
   온도the mixture was cooled
5. 5
   기타the reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate
6. 6
   추출The aqueous layer was extracted with ethyl acetate
7. 7
   건조dried over MgSO4
8. 8
   여과filtered
9. 9
   농축concentrated
10. 10
    기타The crude product was purified by preparative HPLC (acid mode, 20-25% ACN/water gradient)
11. 11
    농축concentrated in vacuo
12. 12
    기타to remove ACN
13. 13
    추출extracted with EtOAc
14. 14
    건조dried over MgSO4
15. 15
    여과filtered
16. 16
    농축concentrated in vacuo

실험 절차

To a 25 mL pear flask were added tert-butyl (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)piperazine-1-carboxylate (0.076 g, 0.21 mmol) and 2,4-diamino-6-chloropyrimidine-5-carbonitrile (0.054 g, 0.32 mmol) in DMSO (1 mL) to give a yellow suspension. Triethylamine (0.088 mL, 0.63 mmol) was added and the mixture was heated to 95° C. for 2 hours. The reaction appeared to stall so 1 equivalent of triethylamine was added. After a total of 4 hours of heating, the mixture was cooled and the reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4, filtered, and concentrated. The crude product was purified by preparative HPLC (acid mode, 20-25% ACN/water gradient). The product-containing fractions were combined, neutralized with a small amount of saturated NaHCO3, concentrated in vacuo to remove ACN, and then extracted with EtOAc. The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as a pale beige solid (37 mg, 36%). 1H NMR (400 MHz, CDCl3) δ ppm 1.43 (s, 11H), 1.87 (br s, 2H), 2.72 (br s, 2H), 2.97 (br s, 2H), 3.70 (s, 3H), 4.80-5.11 (m, 4H), 5.92 (br s, 1H), 6.59 (d, J=2.27 Hz, 1H), 6.76 (d, J=6.06 Hz, 1H), 7.16 (d, J=2.78 Hz, 2H), 7.32 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C24H32N10O2, 493. found 493.

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