Hydrochloric Acid → 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(5-(piperazin-1-ylmethyl)thiophen-2-yl)-1H-isochromen-1-one dihydrochloride

HRID 634490Notes

Reaction equation

HRID 634490 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]([C:22]3[O:23][C:24](=[O:54])[C:25]4[C:30]([C:31]=3[C:32]3[S:36][C:35]([CH2:37][N:38]5[CH2:43][CH2:42][N:41](C(OCC6C=CC=CC=6)=O)[CH2:40][CH2:39]5)=[CH:34][CH:33]=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([O:17]C)[CH:14]=[C:13]([F:19])[CH:12]=3)[C:3]=12.BrB(Br)Br.CO.[ClH:61]>ClCCl.CC#N.O.C(O)=O>[ClH:61].[ClH:61].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]([C:22]3[O:23][C:24](=[O:54])[C:25]4[C:30]([C:31]=3[C:32]3[S:36][C:35]([CH2:37][N:38]5[CH2:39][CH2:40][NH:41][CH2:42][CH2:43]5)=[CH:34][CH:33]=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([OH:17])[CH:14]=[C:13]([F:19])[CH:12]=3)[C:3]=12

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 25134Boron tribromideHCID 118131178benzyl 4-((5-(3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1-oxo-1H-isochromen-4-yl)thiophen-2-yl)methyl)piperazine-1-carboxylate

Product 1

HCID 1181314923-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(5-(piperazin-1-ylmethyl)thiophen-2-yl)-1H-isochromen-1-one dihydrochlorideYield 61.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 86621318Acetonitrile water formic acidSolvent

Procedure

In a 250 ml round bottomed flask equipped with a magnetic stirrer benzyl 4-((5-(3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1-oxo-1H-isochromen-4-yl)thiophen-2-yl)methyl)piperazine-1-carboxylate (460 mg, 0.617 mmol) was suspended in 20 ml of dry dichloromethane then 1M tribromoborane in DCM (5 ml) was added and the mixture was stirred overnight at r.t. MeOH (15 ml) and 1M HCl (5 ml) were added and the mixture was stirred for 30 min then organic solvents were evaporated and the crude was purified by reverse phase chromatography eluting with H2O\MeCN\HCOOH 95:5:0.1% and MeCN\H2O\HCOOH 95:5:0.1%, to give the title compound (254 mg, 0.379 mmol, 61.4% yield) as a whitish solid.

Workup

  1. stirringthe mixture was stirred for 30 min
  2. customorganic solvents were evaporated
  3. customthe crude was purified by reverse phase chromatography
  4. washeluting with H2O\MeCN\HCOOH 95:5

Sources & evidence

ORD record
ord-c254c741618c42deabc3a2be90121e41
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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