N-methylthiophen-3-amine → HCID 68108739, 화합물

HRID 1809740

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HRID 1809740 반응식
[C:1]([O:5][C:6](=[O:39])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[N:25]=4)[C:18]3=[CH:17][N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[S:40]1[CH:44]=[CH:43][C:42](NC)=[CH:41]1.[CH3:47][N:48](C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C(O[Na])(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:1]([O:5][C:6](=[O:39])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([NH:48][CH2:47][C:42]5[CH:43]=[CH:44][S:40][CH:41]=5)[N:25]=4)[C:18]3=[CH:17][N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 642344N-methylthiophen-3-amineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86667966HCID 86667966, 화합물HCID 178418730sodium 2-methylpropan-2-olate

생성물 1

HCID 68108739HCID 68108739, 화합물

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
102 °C

실험 절차

A sealed tube was charged with {4-[3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (from Example 33 supra) (500 mg, 0.809 mmol), thiophen-3-yl-methylamine (118 mg, 1.044 mmol), Pd2(dba)3 (47 mg, 0.0817 mmol), DavePhos (64 mg, 0.163 mmol), t-BuONa (109 mg, 1.135 mmol) and dioxane (20 mL). The mixture was stirred at 102° C. under an atmosphere of N2 for 12 hours. After cooling to room temperature, the mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 12 g, 200-300 mesh, eluting with petroleum ether:ethyl acetate, 3:1) to give {4-[3-{6-[(thiophen-3-ylmethyl)-amino]-pyridin-2-yl}-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester. (Yield 415 mg, 79%).

후처리

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography (silica gel, 12 g, 200-300 mesh, eluting with petroleum ether:ethyl acetate, 3:1)

출처 및 근거

ORD 기록
ord-b92f9d4f68b14fc083baf5c6e44cd737
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362023B2

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