Diisopropylethylamine → (s)-2-Chloro-5-fluoro-n-(1-(5-fluoropyridin-2-yl)ethyl)-6-morpholinopyrimidin-4-amine

HRID 573990노트

반응식

HRID 573990 반응식
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5]([F:14])=[C:4](Cl)[N:3]=1.Cl.[F:17][C:18]1[CH:19]=[CH:20][C:21]([C@@H:24]([NH2:26])[CH3:25])=[N:22][CH:23]=1.CCN(C(C)C)C(C)C>C(O)CCC>[Cl:1][C:2]1[N:3]=[C:4]([NH:26][C@H:24]([C:21]2[CH:20]=[CH:19][C:18]([F:17])=[CH:23][N:22]=2)[CH3:25])[C:5]([F:14])=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 67123789(S)-1-(5-fluoropyridin-2-yl)ethanamine hydrochlorideHCID 866441264-(2,6-Dichloro-5-fluoropyrimidin-4-yl)morpholine

생성물 1

HCID 71612726(s)-2-Chloro-5-fluoro-n-(1-(5-fluoropyridin-2-yl)ethyl)-6-morpholinopyrimidin-4-amine수율 42%

시약·촉매·용매 1

HCID 2631-Butanol용매

반응 조건

온도
130 °C

실험 절차

A mixture of 4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine (Preparation 11a, 1.18 g, 4.68 mmol), (S)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride (prepared as described in WO2006/123113, 1.00 g, 4.69 mmol) and N,N′-diisopropylethylamine (3.27 mL, 18.77 mmol) in n-butanol (20 mL) was heated at 130° C. for two days. The solvent was evaporated under reduced pressure and the residue was purified by flash chromatography (0-5% ethyl acetate in hexanes to 5:94:1 ethyl acetate/hexanes/triethylamine) to give the title compound (0.700 g, 42%) as one major regioisomer. The chemical structures of both regioisomers were confirmed by NMR experiments (gHSQCAD and gHMBCAD).

후처리

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was purified by flash chromatography (0-5% ethyl acetate in hexanes to 5:94:1 ethyl acetate/hexanes/triethylamine)

출처 및 근거

ORD 기록
ord-ff3876748bcf4d1296ed001ef327b465
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034311B2

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