Cesium carbonate → (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime

HRID 1917507노트

반응식

HRID 1917507 반응식
[NH2:1][C:2]1[N:3]=[C:4]([CH3:22])[C:5]2=[C:6]([CH2:8][C@H:9]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[Br:21])[NH:10]/[C:11]/2=[N:12]\[OH:13])[N:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].I[CH2:30][CH2:31][C@H:32]1[CH2:36][O:35][C:34]([CH3:38])([CH3:37])[O:33]1>CN(C=O)C>[CH3:37][C:34]1([CH3:38])[O:33][C@@H:32]([CH2:31][CH2:30][O:13]/[N:12]=[C:11]2\[NH:10][C@@H:9]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[Br:21])[CH2:8][C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([CH3:22])[C:5]\2=3)[CH2:36][O:35]1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 11076039(4S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolaneHCID 178433358HCID 178433358, 화합물

생성물 1

HCID 178433346(R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime수율 63.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (85c, 9.2 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (85d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of the starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered and rinsed with cold water. Drying afforded (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (7.8 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 3H) 1.41 (s, 3H) 2.02 (qd, J=6.32, 3.03 Hz, 2H) 2.75 (s, 3H) 2.94 (dd, J=16.42, 8.84 Hz, 1H) 3.17 (dd, J=16.42, 4.55 Hz, 1H) 3.59 (dd, J=8.08, 7.07 Hz, 1H) 4.09 (dd, J=8.08, 6.06 Hz, 1H) 4.17-4.28 (m, 3H) 4.98 (ddd, J=8.72, 4.55, 1.64 Hz, 1H) 7.07 (td, J=8.27, 2.65 Hz, 1H) 7.34 (dd, J=8.08, 2.78 Hz, 1H) 7.43 (dd, J=8.72, 5.94 Hz, 1H). MS (ES) [M+H] calculated for C21H27BrFN5O3, 495.11; found 495.30.

후처리

  1. stirringthe reaction mixture stirred overnight
  2. customconsumption of the starting material
  3. additionThe reaction mixture was poured
  4. customonto crushed ice
  5. filtrationthe resulting solid was filtered
  6. washrinsed with cold water
  7. customDrying

출처 및 근거

ORD 기록
ord-f7a38ffe57c447c9a20ecc0db0147813
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618290B2

반응 노트

불러오는 중…