Potassium Carbonate → 3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(morpholinomethyl)-1H-isochromen-1-one

HRID 634487Notes

Reaction equation

HRID 634487 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[N:16][C:17]=3[NH2:19])[NH:12][N:11]=2)[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br.Br[CH:28]([C:30]1[O:31][C:32](=[O:47])[C:33]2[C:38]([C:39]=1[CH2:40][N:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1)=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH3:29]>CN(C=O)C>[NH2:19][C:17]1[N:16]=[CH:15][N:14]=[C:13]2[N:12]([CH:28]([C:30]3[O:31][C:32](=[O:47])[C:33]4[C:38]([C:39]=3[CH2:40][N:41]3[CH2:42][CH2:43][O:44][CH2:45][CH2:46]3)=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH3:29])[N:11]=[C:10]([C:4]3[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=[C:2]([F:1])[CH:3]=3)[C:18]=12

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1181315053-(1-bromoethyl)-4-(morpholinomethyl)-1H-isochromen-1-one hydrobromideHCID 178492931HCID 178492931, compound

Product 1

HCID 1181314973-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(morpholinomethyl)-1H-isochromen-1-oneYield 12.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-(3-Fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (intermediate G1, 0.135 g, 0.521 mmol) and potassium carbonate (0.206 g, 1.498 mmol) were mixed in DMF (5 ml) and stirred at r.t. for 10 min. Then a solution of 3-(1-bromoethyl)-4-(morpholinomethyl)-1H-isochromen-1-one hydrobromide (intermediate C48, 0.215 g, 0.496 mmol) in DMF (5 ml) was added and the mixture was heated at 70° C. for 3 hrs. The reaction was quenched by the addition of 1M HCl (2 ml) and the solvent was removed under vacuum. The crude was purified by reverse phase flash chromatography on C18 Biotage cartridge (H2O:CH3CN=80:20 to 100% CH3CN, with 0.1% HCOOH) to afford 3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(morpholinomethyl)-1H-isochromen-1-one (0.033 g).

Workup

  1. temperaturethe mixture was heated at 70° C. for 3 hrs
  2. customThe reaction was quenched by the addition of 1M HCl (2 ml)
  3. customthe solvent was removed under vacuum
  4. customThe crude was purified by reverse phase flash chromatography on C18 Biotage cartridge (H2O:CH3CN=80:20 to 100% CH3CN, with 0.1% HCOOH)

Sources & evidence

ORD record
ord-602da2b439e9432c91ed5f7771a340fd
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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