Sodium Carbonate → 3-(4-aminophenyl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 2365753Notes

Reaction equation

HRID 2365753 reaction equation
[N+](C1C=CC(B(O)O)=CC=1)([O-])=O.IC1C2C(=NC=NC=2N)N(C(C)C)N=1.C(=O)([O-])[O-].[Na+].[Na+].[CH:33]([N:36]1[C:40]2=[N:41][CH:42]=[N:43][C:44]([NH2:45])=[C:39]2[C:38]([C:46]2[CH:51]=[CH:50][C:49]([N+:52]([O-])=O)=[CH:48][CH:47]=2)=[N:37]1)([CH3:35])[CH3:34]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].[Zn].CC(O)=O.C1COCC1.CCO>[NH2:52][C:49]1[CH:50]=[CH:51][C:46]([C:38]2[C:39]3[C:40](=[N:41][CH:42]=[N:43][C:44]=3[NH2:45])[N:36]([CH:33]([CH3:35])[CH3:34])[N:37]=2)=[CH:47][CH:48]=1

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 27735524-Nitrophenylboronic acidHCID 249053373-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 58506748HCID 58506748, compound

Product 1

HCID 585067963-(4-aminophenyl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 178527696HCID 178527696, compoundCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

With reference to Scheme 5, 4-nitrophenyl boronic acid (100 mg, 0.330 mmol; Sigma-Aldrich), was coupled to 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (140 mg, 0.8248 mmol; Apsel et al., 2008) via the Suzuki reaction in 6 mL 1,2 methoxy ethane, 1 mL of saturated sodium carbonate, 1.65 mL EtOH, and 200 mg of polymer-bound tetrakis Palladium. The reaction was stirred under argon for 12 hours at room temperature, filtered through Whatman paper to remove Palladium, mixed with brine, extracted in chloroform and the product was subsequently purified on silica in EtOAc and concentrated in vacuo. The purified solid 1-isopropyl-3-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (ESI-MS m/z [M+H]+ found 299.1, calculated 299.1; 100 mg, 0.336 mmol) was combined with Zinc dust, 5 mL THF, 0.4 mL HOAc for 12 hours at room temperature under Argon. Then the reaction mixture was filtered through Celite®, extracted with EtOAc and concentrated in vacuo to yield 3-(4-aminophenyl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (ESI-MS m/z [M+H]+ found 269.1, calculated 269.1). To this reduced product, molar equivalents of 3-(trifluoromethyl)phenyl isocyanate (Sigma-Aldrich) were added dropwise in ice-cold CH2Cl2. The reaction proceeded until completion as judged by TLC, was concentrated in vacuo, resuspended in 50:50 H20-CH3CN, and purified on a C18 column in CH3CN/H20/0.1% TFA (1-100% gradient) to yield Cmpd 5 1-(4-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea (ESI-MS m/z [M+H]+ found 455.2, calculated 455.2; 1H NMR (400 MHz, DMSO): δ 9.48 (s, 1H), 9.42 (s, 1H), 8.39 (s, 1H), 8.07 (s, 1H), 7.70 (d, J=8 Hz, 2H), 7.60 (d, J=8 Hz, 2H), 7.60-7.64 (m, 1H), 7.53 (t, J=8 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 5.10 (septet, J=6.8 Hz, 1H), 1.51 (d, J=6 Hz, 6H), 3.10 (q, J=4 Hz, 1.5H, trace triethylamine), 1.18 (t, J=8 Hz, 2H, trace triethylamine). 13C NMR (400 MHz, DMSO): δ 9.08 (trace triethylamine), 22.23, 46.20 (trace triethylamine), 49.17, 97.40, 115.45, 116.0 (d), 119.20, 122.34, 124.70 (q), 126.19, 129.35, 130.00 (q), 130.40, 140.85, 141.09, 145.20, 151.70, 152.35, 153.00, 155.72, 159.41 (q)).

Workup

  1. filtrationfiltered through Whatman paper
  2. customto remove Palladium
  3. additionmixed with brine
  4. extractionextracted in chloroform
  5. customthe product was subsequently purified on silica in EtOAc
  6. concentrationconcentrated in vacuo
  7. filtrationThen the reaction mixture was filtered through Celite®
  8. extractionextracted with EtOAc
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-99d2e163b9984a2ea64dbd5e8e3e6749
Source dataset
uspto-grants-2014_04
Patent number
US08697709B2

Reaction notes

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