Diisopropylethylamine → (2R,3R)-3-(tert-butoxy)-2-((6-fluoro-2-(((S)-1-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)ethyl)amino)pyrimidin-4-yl)amino)butan-1-ol

HRID 57475

반응식

HRID 57475 반응식
F[C:2]1[CH:7]=[C:6]([F:8])[N:5]=[C:4]([NH:9][C@H:10]([C:12]2[CH:13]=[N:14][N:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH:16]=2)[CH3:11])[N:3]=1.[NH2:24][C@@H:25]([C@H:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH3:29])[CH2:26][OH:27].C(N(C(C)C)C(C)C)C>CS(C)=O.C(OCC)(=O)C.[Cl-].[Na+]>[C:31]([O:30][C@H:28]([CH3:29])[C@H:25]([NH:24][C:2]1[CH:7]=[C:6]([F:8])[N:5]=[C:4]([NH:9][C@H:10]([C:12]2[CH:13]=[N:14][N:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH:16]=2)[CH3:11])[N:3]=1)[CH2:26][OH:27])([CH3:34])([CH3:32])[CH3:33]

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 87698345(2R,3R)-2-amino-3-(tert-butoxy)butan-1-olHCID 90414038(S)-4,6-difluoro-N-(1-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)ethyl)pyrimidin-2-amine

생성물 1

HCID 90416255(2R,3R)-3-(tert-butoxy)-2-((6-fluoro-2-(((S)-1-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)ethyl)amino)pyrimidin-4-yl)amino)butan-1-ol수율 50.4%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 5234Sodium Chloride용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of (S)-4,6-difluoro-N-(1-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)ethyl)pyrimidin-2-amine (80 mg, 0.25 mmol), (2R,3R)-2-amino-3-(tert-butoxy)butan-1-ol (55 mg, 0.28 mmol, 1.1 equiv), and N-ethyl-N-isopropylpropan-2-amine (0.11 mL, 0.63 mmol, 2.5 equiv) in DMSO (1.3 mL) was heated at 85° C. for 16 hours. The reaction was cooled to room temperature and diluted with ethyl acetate (30 mL) and dilute aqueous sodium chloride (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane) provided (2R,3R)-3-(tert-butoxy)-2-((6-fluoro-2-(((S)-1-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)ethyl)amino)pyrimidin-4-yl)amino)butan-1-ol (0.058 g, white solid) in 50% yield. 1H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.66 (s, 1H), 7.61 (m, 2H), 7.13 (t, J=8.6 Hz, 2H), 5.35 (s, 1H), 5.30-5.14 (m, 2H), 5.04 (m, 1H), 3.94 (m, 1H), 3.77-3.65 (m, 2H), 1.57 (d, J=6.9 Hz, 3H), 1.21 (s, 9H), 1.15 (d, J=6.0 Hz, 3H). MS m/z 461.3 (M+H)+; Rt-0.88 min.

후처리

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (20 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-017e1f87c813466585d0d3d9e2e4e694
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434719B2

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