Sodium Carbonate → 1-isopropyl-3-(2-(methylamino)benzo[d]thiazol-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 880525Notes

Reaction equation

HRID 880525 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]([CH3:14])[CH3:13])[N:3]=1.[CH3:15][NH:16][C:17]1[S:18][C:19]2[CH:25]=[C:24](B3OC(C)(C)C(C)(C)O3)[CH:23]=[CH:22][C:20]=2[N:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCO.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:12]([N:4]1[C:5]2=[N:6][CH:7]=[N:8][C:9]([NH2:11])=[C:10]2[C:2]([C:24]2[CH:23]=[CH:22][C:20]3[N:21]=[C:17]([NH:16][CH3:15])[S:18][C:19]=3[CH:25]=2)=[N:3]1)([CH3:14])[CH3:13]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 249053373-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 58279591N-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-amine2×

Product 1

HCID 866537311-isopropyl-3-(2-(methylamino)benzo[d]thiazol-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 34.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (104) (47 mg, 0.16 mmol), N-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-amine (703 (37 mg, 0.13 mmol), Pd(OAc)2 (6 mg, 0.027 mmol), triphenyl phosphine (20 mg, 0.076 mmol) and Na2CO3 (69 mg, 0.65 mmol) was dissolved in a mixture of DMF (4 mL), EtOH (4 mL) and H2O (2 mL). The resulting mixture was degassed and back-filled with argon three times and then stirred at 90° C. for 1.5 h. The mixture was allowed to cool to room temperature and filtered. The filtrate was concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (200-300 mesh) eluting with DCM/MeOH (20/1) to give the desired product 1-isopropyl-3-(2-(methylamino)benzo[d]thiazol-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (704) (15 mg, 34.1%) as a pale solid. ESI-MS (M+H)+ m/z: 340.05.

Workup

  1. customThe resulting mixture was degassed
  2. additionback-filled with argon three times
  3. temperatureto cool to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel (200-300 mesh)
  7. washeluting with DCM/MeOH (20/1)

Sources & evidence

ORD record
ord-e4061b5f0563459abff8889810b27211
Source dataset
uspto-grants-2015_03
Patent number
US08993580B2

Reaction notes

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