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 516143노트

반응식

HRID 516143 반응식
[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

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-1dc068db2d49478cb84de54f4cb190b5
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108973B2

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