Water → 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(5-(piperidin-1-ylmethyl)thiophen-2-yl)-1H-isochromen-1-one hydrochloride

HRID 634468노트

반응식

HRID 634468 반응식
[ClH:1].[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:13]([C:15]3[O:16][C:17](=[O:37])[C:18]4[C:23]([C:24]=3[C:25]3[S:26][C:27]([CH2:30][N:31]5[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]5)=[CH:28][CH:29]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH3:14])[N:10]=[C:11](I)[C:4]=12.[F:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[C:43]([OH:45])[CH:44]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>C1COCC1>[ClH:1].[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:13]([C:15]3[O:16][C:17](=[O:37])[C:18]4[C:23]([C:24]=3[C:25]3[S:26][C:27]([CH2:30][N:31]5[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]5)=[CH:28][CH:29]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH3:14])[N:10]=[C:11]([C:41]3[CH:42]=[C:43]([OH:45])[CH:44]=[C:39]([F:38])[CH:40]=3)[C:4]=12

참가 물질

6

반응물 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 1181314303-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(5-(piperidin-1-ylmethyl)thiophen-2-yl)-1H-isochromen-1-one hydrochloride2회

생성물 1

HCID 1181314513-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(5-(piperidin-1-ylmethyl)thiophen-2-yl)-1H-isochromen-1-one hydrochloride수율 71.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(5-(piperidin-1-ylmethyl)thiophen-2-yl)-1H-isochromen-1-one hydrochloride (Intermediate D9, 100 mg, 0.154 mmol), 3-fluoro-5-hydroxyphenylboronic acid (48.1 mg, 0.308 mmol), S-Phos-Pd-G2 (11.10 mg, 0.015 mmol) and K3PO4 (151 mg, 0.462 mmol) were reacted in THF (1.2 ml) and water (0.3 ml) under argon at 80° C. under mw irradiation for 30 min The reaction was quenched by the addition of 1M HClaqueous (2 ml) and the mixture purified via reverse phase chromatography using a Biotage C18 60 g SNAP with a gradient of water and acetonitrile to give (prior to drying a small amount of 1M HCl aqueous was added) the title compound (70 mg, 71.7% yield) as yellowish solid.

후처리

  1. customwas quenched by the addition of 1M HClaqueous (2 ml)
  2. customthe mixture purified via reverse phase chromatography
  3. customto give (prior
  4. dry with materialto drying a small amount of 1M HCl aqueous

출처 및 근거

ORD 기록
ord-d9535acaf00d487aae1acb53c463394c
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321776B2

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