Chlorocyclohexane → HCID 67470905, compound

HRID 928239

Reaction equation

HRID 928239 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([NH:11][CH2:12][CH2:13][CH3:14])=[N:8][CH:9]=2)[NH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH:21]1(Cl)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>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.O.CN(C=O)C>[CH:21]1([N:4]2[C:5]3=[N:6][C:7]([NH:11][CH2:12][CH2:13][CH3:14])=[N:8][CH:9]=[C:10]3[C:2]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:3]2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

8

Reactant 4

HCID 10952ChlorocyclohexaneHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 178456834HCID 178456834, compound

Product 1

HCID 67470905HCID 67470905, compoundYield 67.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
200 °C

Procedure

A 10 mL microwave tube was charged with 3-bromo-N-propyl-1H-pyrazolo[3,4-d]pyrimidin-6-amine (0.052 g, 0.2 mmol), K2CO3 (0.14 g, 1.0 mmol), DMF (2 mL), and cyclohexyl chloride (0.072 g, 0.6 mmol). The resulting mixture was heated at 200° C. for 30 minutes under microwave irradiation. After the reaction was cooled to room temperature, phenylboronic acid (0.37 g, 0.3 mmol), Pd(PPh3)4 (0.023 g, 0.02 mmol), and H2O (1 mL) were added sequentially. The mixture was stirred at room temperature for 3 min and then heated at 150° C. for 15 min. After cooled to room temperature, the mixture was partitioned in H2O and Et2O. The aqueous phase was extracted with ether (3×). The combined organic phase were dried (Na2SO4) and concentrated. The residue was purified by Isco to provide the 1-cyclohexyl-3-phenyl-N-propyl-1H-pyrazolo[3,4-d]pyrimidin-6-amine (UNC702A) (0.045 g, 67%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 7.90 (d, J=8.0 Hz, 2H), 7.48 (t, J=6.0 Hz, 2H), 7.38 (t, J=6.0 Hz, 1H), 5.42 (s, 1H), 4.60 (tt, J=11.6, 4.1 Hz, 1H), 3.48 (dt, J=13.1, 6.8 Hz, 2H), 2.18-2.08 (m, 2H), 2.04-2.00 (m, 2H), 1.95-1.92 (m, 2H), 1.77-1.74 (m, 1H), 1.74-1.65 (m, 2H), 1.58-1.42 (m, 2H), 1.40-1.28 (m, 1H), 1.03 (t, J=7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 160.73, 155.38, 153.50, 143.71, 133.27, 129.06, 128.60, 127.09, 106.91, 56.10, 43.68, 32.16, 25.91, 25.61, 22.98, 11.77; MS m/z 336.2 [M+1].

Workup

  1. temperatureAfter the reaction was cooled to room temperature
  2. temperatureheated at 150° C. for 15 min
  3. temperatureAfter cooled to room temperature
  4. customthe mixture was partitioned in H2O
  5. extractionThe aqueous phase was extracted with ether (3×)
  6. dry with materialThe combined organic phase were dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified by Isco

Sources & evidence

ORD record
ord-a7f2c8f0cacb4db8a4003745e6eadd6e
Source dataset
uspto-grants-2016_03
Patent number
US09290499B2

Linked notes

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