Hydrochloric Acid → 3-(1-(4-amino-3-(3-(benzyloxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one

HRID 634416Notes

Reaction equation

HRID 634416 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[C:24]3[C:19](=[N:20][CH:21]=[N:22][C:23]=3[NH2:25])[NH:18][N:17]=2)[CH:12]=[C:13]([F:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:33]([C:35]1[O:36][C:37](=[O:60])[C:38]2[C:43]([C:44]=1[C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([CH:51]3[O:55][C:54]([CH3:57])([CH3:56])[C:53]([CH3:59])([CH3:58])[O:52]3)[CH:46]=1)=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH3:34].Cl>CN(C=O)C.CCOC(C)=O>[NH2:25][C:23]1[N:22]=[CH:21][N:20]=[C:19]2[N:18]([CH:33]([C:35]3[O:36][C:37](=[O:60])[C:38]4[C:43]([C:44]=3[C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([CH:51]5[O:52][C:53]([CH3:59])([CH3:58])[C:54]([CH3:57])([CH3:56])[O:55]5)[CH:46]=3)=[CH:42][CH:41]=[CH:40][CH:39]=4)[CH3:34])[N:17]=[C:16]([C:11]3[CH:12]=[C:13]([F:15])[CH:14]=[C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:10]=3)[C:24]=12

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 1181311093-(1-bromoethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-oneHCID 1785087223-(3-(benzyloxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 1181311553-(1-(4-amino-3-(3-(benzyloxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-oneYield 0.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

In a 100 ml round bottomed flask 3-(3-(benzyloxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate G18, 400 mg, 1,194 mmol) was dissolved in 7 ml of dry DMF then K2CO3 (254 mg, 1.837 mmol) was added. After stirring for 5 min a solution of 3-(1-bromoethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one (Intermediate C26, 420 mg, 0,918 mmol) in 7 ml of dry DMF was added and the clear brown mixture was heated at 60° C. for 30 min. The mixture was cooled to r.t. then 30 ml of HCl 0.5 M and 50 ml of EtOAc were added and stirred for 15 min. Phases were separated and the crude material was purified by chromatography eluting with DCM\MeOH (80/20) in DCM to give the title compound (820 mg) as a brown oil. This material was used in the next step without any further purification.

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled to r.t.
  3. customPhases were separated
  4. customthe crude material was purified by chromatography
  5. washeluting with DCM\MeOH (80/20) in DCM

Sources & evidence

ORD record
ord-018fe8fe0e594690a89d9b5adf006e67
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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