Water → 2-{[1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}-3-methoxy-N-(5-methylpyridin-2-yl)propanamide

HRID 1097980ノート

反応式

HRID 1097980 の反応式
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[OH:11][CH:12]([CH2:23][O:24][CH3:25])[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=1)=[O:14].Cl[C:27]1[N:32]=[CH:31][N:30]=[C:29]2[N:33]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[Cl:42])[N:34]=[CH:35][C:28]=12.O>C1COCC1.CCOC(C)=O>[Cl:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[N:33]1[C:29]2=[N:30][CH:31]=[N:32][C:27]([O:11][CH:12]([CH2:23][O:24][CH3:25])[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=3)=[O:14])=[C:28]2[CH:35]=[N:34]1

参加物

7

反応物 4

HCID 962WaterHCID 2733832Lithium Hexamethyldisilazide2 回HCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidineHCID 57438612HCID 57438612、化合物

生成物 1

HCID 575042462-{[1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}-3-methoxy-N-(5-methylpyridin-2-yl)propanamide収率 77.4%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

LHMDS (1.40 mL, 1.0 M in THF, 1.40 mmol) was added slowly to a stirred solution of 2-hydroxy-3-methoxy-N-(5-methylpyridin-2-yl)propanamide (200 mg, 0.951 mmol) in anhydrous THF (5 mL). The reaction mixture was kept at ambient temperature for 10 minutes, and a solution of 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (265 mg, 1.00 mmol) in anhydrous THF (3 mL) was added. The reaction mixture was heated at 50° C. for ½ hrs (another 3 equivalents of LHMDS were added and the reaction heated for 18 hrs at 50° C. in example 49). Water and EtOAc were added, and the two phases were separated. The organic phase was washed with water, dried over MgSO4 and concentrated in vacuo. The residue was purified with column chromatography (silica gel, eluting with DCM/EtOAc:2/1) to give the title compound as a colourless solid (323 mg), 1H NMR (500 MHz, CDCl3) δ 8.67 (br s, 1H), 8.62 (s, 1H), 8.48 (s, 1H), 8.18 (d, 1H), 8.12 (s, 1H), 7.65 (d, 1H), 7.52 (m, 4H), 6.13 (t, 1H), 4.14 (m, 2H), 4.06 (m, 1H), 3.49 (s, 3H), 2.32 (s, 3H), HRMS: calcd for (M+H+) C21H2035ClN6O3: 439.1285. Found: 439.1287.

後処理

  1. additionwere added
  2. customthe two phases were separated
  3. washThe organic phase was washed with water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified with column chromatography (silica gel, eluting with DCM/EtOAc:2/1)

出典と根拠

ORDレコード
ord-06bfb32d916c4c68b7f421cc7f2e0dbb
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

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