Trifluoroacetic acid → 1-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-butan-2-one

HRID 719477

반응식

HRID 719477 반응식
Cl.[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]3=[N:17][CH:18]=[N:19][C:20]([O:21][CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)=[C:15]3[CH:14]=[N:13]2)=[CH:8][CH:7]=1)(=[O:5])=[O:4].CCN(CC)CC.[CH2:35]([C:37]([CH2:39]Br)=[O:38])[CH3:36].C(O)(C(F)(F)F)=O>O1CCOCC1.CC#N.O>[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]3=[N:17][CH:18]=[N:19][C:20]([O:21][CH:22]4[CH2:27][CH2:26][N:25]([CH2:39][C:37](=[O:38])[CH2:35][CH3:36])[CH2:24][CH2:23]4)=[C:15]3[CH:14]=[N:13]2)=[CH:8][CH:7]=1)(=[O:4])=[O:5]

참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acid2회HCID 8471TriethylamineHCID 131561-Bromo-2-butanoneHCID 218977741-(4-Methanesulfonyl-phenyl)-4-(piperidin-4-yloxy)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride

생성물 1

HCID 218974891-{4-[1-(4-Methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidin-1-yl}-butan-2-one수율 19%

시약·촉매·용매 3

HCID 962Water용매2회HCID 6342Acetonitrile용매3회HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

To a solution of 1-(4-methanesulfonyl-phenyl)-4-(piperidin-4-yloxy)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride (30.0 mg, 0.073 m mmol) and Et3N (35 μL) in dioxane (1.5 mL) was added bromomethyl ethyl ketone (22 μL, 0.219 mmol). The mixture was heated by microwave irradiation at 100° C. for 10 min. The mixture was diluted with CH3CN (3 mL) and purified by reverse-phase HPLC: Phenomenex® Luna C18 column (10μ, 250×21.2 mm), 5% (v/v) CH3CN (containing 1% v/v TFA) in H2O (containing 1% v/v TFA) gradient to 95% H2O, 20 mL/min, λ=214 nm to give Compound A168 (7.8 mg, 0.014 mmol, 19% yield) isolated as a white solid. HPLC/MS: Alltech® Prevail C18 column (5μ, 50×4.6 mm), 5% v/v CH3CN (containing 1% v/v TFA) in H2O (containing 1% v/v TFA) gradient to 99% v/v CH3CN in H2O, 3.5 mL/min, tr=1.69 min, ESI+=444.3 (M+H).

후처리

  1. custompurified by reverse-phase HPLC
  2. additionPhenomenex® Luna C18 column (10μ, 250×21.2 mm), 5% (v/v) CH3CN (containing 1% v/v TFA) in H2O (
  3. additioncontaining 1% v/v TFA) gradient to 95% H2O, 20 mL/min, λ=214 nm
  4. customto give Compound A168 (7.8 mg, 0.014 mmol, 19% yield)
  5. customisolated as a white solid

출처 및 근거

ORD 기록
ord-04371e20a23f4e7b80a74606a1d3abcf
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07132426B2

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