HCID 45257321, 화합물 → (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 1917482노트

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HRID 1917482 반응식
[NH2:1][C:2]1[N:3]=[C:4]([CH3:21])[C:5]2[C:11](=S)[NH:10][C@@H:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[Br:20])[CH2:8][C:6]=2[N:7]=1.[CH3:22][C:23]1([CH3:32])[O:27][C@@H:26]([CH2:28][CH2:29][O:30][NH2:31])[CH2:25][O:24]1>[Hg](OC(C)=O)OC(C)=O.C1(C)C=CC=CC=1>[CH3:22][C:23]1([CH3:32])[O:27][C@@H:26]([CH2:28][CH2:29][O:30]/[N:31]=[C:11]2\[NH:10][C@@H:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[Br:20])[CH2:8][C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([CH3:21])[C:5]\2=3)[CH2:25][O:24]1

참가 물질

5

반응물 2

HCID 45257321HCID 45257321, 화합물HCID 57999036(S)-O-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)hydroxylamine

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 65%

시약·촉매·용매 2

HCID 16683746Diacetyloxymercury촉매HCID 1140Toluene용매

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온도
100 °C

실험 절차

A mixture of (R)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidine-5(6H)-thione (311,100 mg, 0.3 mmol), (S)—O-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)hydroxylamine (194 mg, 1.2 mmol), Hg(OAc)2 (192 mg, 0.6 mmol) and anhydrous toluene (2 mL) was heated at 100° C. for 1 h. LCMS shows completion of the reaction. The mixture was cooled, filtered through celite and washed with ethyl acetate. Filtrate concentrated and the resulting oily residue was purified by preparative LCMS to afford (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 (35A, 87 mg, 65%) as a pale yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 1.35 (s, 3H) 1.40 (s, 3H) 2.01 (qd, J=6.32, 3.03 Hz, 2H) 2.76 (s, 3H) 2.95 (dd, J=16.42, 8.84 Hz, 1H) 3.18 (dd, J=17.18, 5.05 Hz, 1H) 3.56-3.62 (m, 1H) 4.09 (dd, J=7.96, 5.94 Hz, 1H) 4.16-4.28 (m, 2H) 4.98 (ddd, J=8.78, 4.61, 1.52 Hz, 1H) 7.07 (td, J=8.21, 2.53 Hz, 1H) 7.34 (dd, J=8.08, 2.53 Hz, 1H) 7.68 (dd, J=12.00, 6.95 Hz, 1H). MS (ES) [M+H] calculated for C2iH26BrFN5O3, 494.11; found 494.00.

후처리

  1. customcompletion of the reaction
  2. temperatureThe mixture was cooled
  3. filtrationfiltered through celite
  4. washwashed with ethyl acetate
  5. concentrationFiltrate concentrated
  6. customthe resulting oily residue was purified by preparative LCMS

출처 및 근거

ORD 기록
ord-7894d8e95abf445488034db07ecd9550
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618290B2

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