3-(Trimethylsilyl)propionic acid → (S)-1-(3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)prop-2-yn-1-one

HRID 516143ノート

反応式

HRID 516143 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:23]3[CH2:27][CH2:26][N:25]([C:28](OC(C)(C)C)=[O:29])[CH2:24]3)[N:9]=[C:10]([C:11]#[C:12][C:13]3[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=3)[C:3]=12.C[Si](C)(C)[CH2:37][CH2:38]C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:23]3[CH2:27][CH2:26][N:25]([C:28](=[O:29])[C:37]#[CH:38])[CH2:24]3)[N:9]=[C:10]([C:11]#[C:12][C:13]3[CH:14]=[C:15]([O:21][CH3:22])[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=3)[C:3]=12

参加物

8

反応物 5

HCID 797643-(Trimethylsilyl)propionic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89870805(S)-tert-butyl 3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidine-1-carboxylate

生成物 1

HCID 89871044(S)-1-(3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)prop-2-yn-1-one

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

The crude product (16 mg) of (S)-3-((3,5-dimethoxyphenyl)ethynyl)-1-(pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine obtained in Example 2 as an intermediate, 3-(trimethylsilyl)propionic acid (10 mg), HATU (28 mg) were dissolved in DMF (0.5 ml). DIPEA (31 μl) was added thereto, followed by stirring overnight. Ethyl acetate and a saturated aqueous sodium bicarbonate solution were added to the reaction mixture to separate the organic layer. After drying the organic layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain the title compound as a white solid (0.7 mg). Table 1 shows the physical properties thereof.

後処理

  1. customto separate the organic layer
  2. dry with materialAfter drying the organic layer over anhydrous sodium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol)

出典と根拠

ORDレコード
ord-1dc068db2d49478cb84de54f4cb190b5
出典データセット
uspto-grants-2015_08
特許番号
US09108973B2

反応ノート

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