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 634468Notes

Reaction equation

HRID 634468 reaction equation
[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

Participants

6

Reactant 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 hydrochloride2×

Product 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 hydrochlorideYield 71.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d9535acaf00d487aae1acb53c463394c
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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