HCID 45257321、化合物 → (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 1917482ノート

反応式

HRID 1917482 の反応式
[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

参加物

5

反応物 2

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

生成物 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 oxime収率 65%

試薬・触媒・溶媒 2

HCID 16683746Diacetyloxymercury触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-7894d8e95abf445488034db07ecd9550
出典データセット
uspto-grants-2013_12
特許番号
US08618290B2

反応ノート

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