Ammonia → 4-amino-6-((S)-1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile

HRID 1019804

반응식

HRID 1019804 반응식
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C@@H:18]([NH2:20])[CH3:19])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.Cl[C:22]1[C:27]([C:28]#[N:29])=[C:26](Cl)[N:25]=[CH:24][N:23]=1.C([N:34](CC)C(C)C)(C)C.N>C1COCC1.O1CCOCC1>[NH2:34][C:22]1[C:27]([C:28]#[N:29])=[C:26]([NH:20][C@H:18]([C:7]2[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9][C:10]3[C:5]([CH:6]=2)=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=3)[CH3:19])[N:25]=[CH:24][N:23]=1

참가 물질

7

반응물 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 5993714,6-Dichloropyrimidine-5-carbonitrileHCID 86698506(S)-1-(7-Fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethan-1-amine

생성물 1

HCID 717659164-amino-6-((S)-1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile수율 15.4%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 312751,4-Dioxane용매

실험 절차

A mixture of (S)-1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethanamine (85 mg, 0.32 mmol), 4,6-dichloro-5-cyanopyrimidine (55 mg, 0.32 mmol, 1.0 eq) and N,N-diisopropylethylamine (68 μl, 0.38 mmol, 1.2 eq) in THF (3 mL) was stirred at rt for 30 min before heating to 50° C. After 4 h, the mixture was concentrated and purified by column chromatography (EtOAc/1/1) to give a white solid, which was treated with saturated NH3 in dioxane (3 mL) in sealed tube at 110° C. overnight. The reaction mixture was concentrated and purified by reverse phase HPLC (MeCN/H2O/0.1% TFA) and lyophilized to give a white powder 4-amino-6-((S)-1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile (19 mg, 15%). 1H NMR (500 MHz, CD3OD) δ ppm 1.78 (d, J=6.85 Hz, 3H) 5.82 (q, J=6.85 Hz, 1H) 7.71 (td, J=8.80, 2.45 Hz, 1H) 7.89 (dd, J=9.66, 2.32 Hz, 1H) 8.10 (ddd, J=7.83, 5.62, 0.98 Hz, 1H) 8.19 (s, 1H) 8.27 (dd, J=9.05, 5.87 Hz, 1H) 8.45 (d, J=7.83 Hz, 1H) 8.63 (td, J=7.95, 1.47 Hz, 1H) 8.94 (s, 1H) 9.03-9.09 (m, 1H). Mass Spectrum (ESI) m/e=386 (M+1).

후처리

  1. temperaturebefore heating to 50° C
  2. waitAfter 4 h
  3. concentrationthe mixture was concentrated
  4. custompurified by column chromatography (EtOAc/1/1)
  5. customto give a white solid, which
  6. concentrationThe reaction mixture was concentrated
  7. custompurified by reverse phase HPLC (MeCN/H2O/0.1% TFA)

출처 및 근거

ORD 기록
ord-0407873ed1b941b593b92e589e6e4a37
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716290B2

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