Potassium Carbonate → 3-(1-(4-amino-3-(2-aminopyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one

HRID 634460Notes

Reaction equation

HRID 634460 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16](=[O:30])[C:17]4[C:22]([C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.C([O-])([O-])=O.[K+].[K+].[NH2:37][C:38]1[N:43]=[CH:42][C:41](B(O)O)=[CH:40][N:39]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16](=[O:30])[C:17]4[C:22]([C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH3:13])[N:9]=[C:10]([C:41]3[CH:40]=[N:39][C:38]([NH2:37])=[N:43][CH:42]=3)[C:3]=12

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 17750211(2-Aminopyrimidin-5-yl)boronic acidHCID 1181310533-(1-(4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one

Product 1

HCID 1181313053-(1-(4-amino-3-(2-aminopyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-oneYield 28.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one (Intermediate D2a, 60 mg, 0.118 mmol), K2CO3 (32.6 mg, 0.236 mmol), 2-aminopyrimidin-5-ylboronic acid (32.7 mg, 0.236 mmol) and Pd(dppf)Cl2 (4.31 mg, 5.89 μmol) were reacted in 2 ml of dioxane, purged with argon and heated overnight at 120° C. The reaction was quenched by the addition of 1M HClaqueous (2 ml) and the resulting mixture was straightforward purified via reverse phase chromatography using a Biotage C18 30 g SNAP with a gradient of water and acetonitrile (prior to drying 2 ml of 1M HClaqueous were added) to give the title compound (16.2 mg, 28.9%) as a yellow solid.

Workup

  1. custompurged with argon
  2. customThe reaction was quenched by the addition of 1M HClaqueous (2 ml)
  3. customthe resulting mixture was straightforward purified via reverse phase chromatography
  4. customto drying 2 ml of 1M HClaqueous
  5. additionwere added)

Sources & evidence

ORD record
ord-329b2ba414ca41488d63c1b525f4c2c9
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

Loading…