Cyclopentylamine → N-Cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-8-amine

HRID 456693

反応式

HRID 456693 の反応式
Cl[C:2]1[C:3]2[N:4]([C:8]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)[N:19]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C.[CH:88]1([NH2:93])[CH2:92][CH2:91][CH2:90][CH2:89]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:88]1([NH:93][C:2]2[C:3]3[N:4]([C:8]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]5[CH2:29][CH2:28][CH2:27][CH2:26]5)[N:19]=4)=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[N:10]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:92][CH2:91][CH2:90][CH2:89]1

参加物

8

反応物 5

HCID 2906CyclopentylamineHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 102014694-[8-Chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-cyclopentylpyrimidin-2-amine

生成物 1

HCID 10161456N-Cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-8-amine収率 55%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

To a solution of 4-[8-chloro-2-(4-fluorophenyl)imidazo[1,2-α]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (200 mg, 0.49 mmol) in cyclopentylamine (10 mL) was added, successively, racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (91 mg, 0.15 mmol), cesium carbonate (0.24 g, 0.7 mmol) and palladium(II) acetate (22 mg, 0.1 mmol). The resulting mixture was heated in a sealed tube at 100° C. for 18 hours at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and ethyl acetate and water were added. The phases were separated and the organic layer was washed with water and brine. The combined organics were dried (magnesium sulfate), filtered and concentrated to a solid. This solid was purified by silica gel chromatography (1:1 hexanes:ethyl acetate) to give N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)imidazo[1,2-α]pyridin-8-amine (120 mg, 55%) as a solid. 1H NMR (CDCl3) δ 8.80 (d, 1H), 8.06 (d, 1H), 7.62 (q, 2H), 7.10 (t, 2H), 6.76 (t, 1H), 6.34 (d, 1H), 6.27 (d, 1H), 5.22 (d, 2H), 4.34 (m, 1H), 3.93 (m, 1H), 2.0–2.1 (m, 4H), 1.4–1.9 (m, 12H); 19F NMR (CDCl3) δ −113.9; MS m/z 457 (M+1).

後処理

  1. temperatureThe solution was cooled to room temperature
  2. customThe phases were separated
  3. washthe organic layer was washed with water and brine
  4. dry with materialThe combined organics were dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated to a solid
  7. customThis solid was purified by silica gel chromatography (1:1 hexanes:ethyl acetate)

出典と根拠

ORDレコード
ord-f800a20d6bfc415b8df42aaa962eac75
出典データセット
uspto-grants-2007_03
特許番号
US07186714B2

関連ノート

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