Triethylamine → (S)-1-(3-(4-amino-3-((3-methoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one

HRID 516190

반응식

HRID 516190 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:12]3[CH2:16][CH2:15][N:14]([C:17](=[O:24])[CH:18]=[CH:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH2:13]3)[N:9]=[C:10](I)[C:3]=12.[C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=1)#[CH:26].C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C.CO.[Cu]I>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:12]3[CH2:16][CH2:15][N:14]([C:17](=[O:24])[CH:18]=[CH:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH2:13]3)[N:9]=[C:10]([C:26]#[C:25][C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=3)[C:3]=12

참가 물질

8

반응물 3

HCID 8471TriethylamineHCID 6407531-Ethynyl-3-methoxybenzeneHCID 131733331(S)-1-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one

생성물 1

HCID 123457045(S)-1-(3-(4-amino-3-((3-methoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 887Methanol용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

PdCl2(dppf)CH2Cl2 (1.3 mg) was added to a mixture of (S)-1-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one (8.0 mg) obtained in Step 1, 1-ethynyl-3-methoxybenzene (4.0 mg), copper (I) iodide (0.6 mg), and triethylamine (8.6 μl) in THF (1.0 ml). After nitrogen purging, the resulting mixture was stirred at 80° C. overnight. The reaction mixture was diluted with ethyl acetate and methanol. The resulting diluted solution was treated with basic silica gel, and then concentrated. The resulting residue was purified by reversed-phase HPLC purification (water/acetonitrile (0.1% formic acid)) to obtain the title compound as a colorless, amorphous substance (1.4 mg). Table 2 shows the physical properties thereof.

후처리

  1. additionThe resulting diluted solution was treated with basic silica gel
  2. concentrationconcentrated
  3. customThe resulting residue was purified by reversed-phase HPLC purification (water/acetonitrile (0.1% formic acid))

출처 및 근거

ORD 기록
ord-9fed6ca33cbe4b04a77c6b1b647a1dad
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108973B2

연결된 노트

불러오는 중…