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

反応式

HRID 57475 の反応式
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]

参加物

7

反応物 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

生成物 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-ol収率 50.4%

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 5234Sodium Chloride溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-017e1f87c813466585d0d3d9e2e4e694
出典データセット
uspto-grants-2016_09
特許番号
US09434719B2

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