Sulfur, trifluoro(N-methylmethanaminato)- → 9-(1-fluoro-2-morpholinoethyl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

HRID 926126노트

반응식

HRID 926126 반응식
CN(S(F)(F)[F:5])C.O[CH:9]([C:17]1[CH:26]=[N:25][C:24]2[N:23]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[C:22](=[O:36])[N:21]3[N:37]=[CH:38][N:39]=[C:20]3[C:19]=2[CH:18]=1)[CH2:10][N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1>C(#N)C.C(=O)(O)[O-].[Na+]>[F:5][CH:9]([C:17]1[CH:26]=[N:25][C:24]2[N:23]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[C:22](=[O:36])[N:21]3[N:37]=[CH:38][N:39]=[C:20]3[C:19]=2[CH:18]=1)[CH2:10][N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1

참가 물질

5

반응물 2

HCID 123203Sulfur, trifluoro(N-methylmethanaminato)-2회HCID 727063249-(1-hydroxy-2-morpholinoethyl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

생성물 1

HCID 867053969-(1-fluoro-2-morpholinoethyl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
60 °C

실험 절차

(Dimethylamino)sulfur trifluoride (0.010 mL, 0.18 mmol) was added to a stirred solution of 9-(1-hydroxy-2-morpholinoethyl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one (Example 83, 49 mg, 0.090 mmol) in ACN (1 mL). After 4 h, additional (dimethylamino)sulfur trifluoride (0.035 mL, 0.36 mmol) was added and the mixture was stirred at 60° C. for 20 h, and cooled to room temperature. The reaction mixture was diluted with aqueous sodium bicarbonate (3 mL) and extracted with DCM (2×3 mL). The combined organic layers were concentrated under a stream of nitrogen and the residue was taken up in methanol, and filtered. Purification (HPLC, 10-75% ACN in water) afforded the title compound but retained impurities. The product was diluted with aqueous sodium bicarbonate (3 mL) and extracted with DCM (2×3 mL). The combined organic layers were concentrated under a stream of nitrogen. Purification (FCC, SiO2, 0 to 40%, IPA/EtOAc) afforded the title compound (9 mg, 21%) as a white powder. 1H NMR (400 MHz, CDCl3) δ 2.58-2.72 (m, 4H), 2.82 (ddd, J=27.98, 13.93, 3.39 Hz, 1H), 3.01 (ddd, J=18.85, 14.15, 7.53 Hz, 1H), 3.72-3.76 (m, 4H), 3.76 (s, 3H), 5.75 (s, 2H), 5.84 (d, J=47.93 Hz, 1H), 6.76-6.88 (m, 2H), 7.60 (d, J=8.66 Hz, 2H), 8.36 (s, 1H), 8.64 (d, J=1.88 Hz, 1H), 8.80 (s, 1H). [M+H]=439.1.

후처리

  1. temperaturecooled to room temperature
  2. extractionextracted with DCM (2×3 mL)
  3. concentrationThe combined organic layers were concentrated under a stream of nitrogen
  4. filtrationfiltered
  5. customPurification (HPLC, 10-75% ACN in water)

출처 및 근거

ORD 기록
ord-2ebc4e76e0e44cdcade08a4352074879
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284335B2

반응 노트

불러오는 중…