Water → 4-{4-[4-(azetidin-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-1-methyl-1H-pyrazol-5-yl}benzaldehyde

HRID 72727Notes

Reaction equation

HRID 72727 reaction equation
[N:1]1([C:5]2[N:10]=[CH:9][N:8]=[C:7]3[N:11]([CH3:21])[N:12]=[C:13]([C:14]4[CH:15]=[N:16][N:17]([CH3:20])[C:18]=4Br)[C:6]=23)[CH2:4][CH2:3][CH2:2]1.[CH:22]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)=[O:23].C(=O)([O-])[O-].[Na+].[Na+].O>C(O)C.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>[N:1]1([C:5]2[N:10]=[CH:9][N:8]=[C:7]3[N:11]([CH3:21])[N:12]=[C:13]([C:14]4[CH:15]=[N:16][N:17]([CH3:20])[C:18]=4[C:27]4[CH:28]=[CH:29][C:24]([CH:22]=[O:23])=[CH:25][CH:26]=4)[C:6]=23)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 711142934-(azetidin-1-yl)-3-(5-bromo-1-methyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 867125724-{4-[4-(azetidin-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-1-methyl-1H-pyrazol-5-yl}benzaldehyde

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

4-(Azetidin-1-yl)-3-(5-bromo-1-methyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (C28) (345 mg, 0.991 mmol), (4-formylphenyl)boronic acid (163 mg, 1.09 mmol), tetrakis(triphenylphosphine)palladium(0) (11.6 mg, 0.0100 mmol), and sodium carbonate (210 mg, 1.98 mmol) were combined in ethanol (10 mL). Water (2 mL) was added, and the reaction mixture was allowed to stir for 18 hours at 100° C. The reaction mixture was concentrated in vacuo and diluted with water. The aqueous layer was extracted with ethyl acetate (3×100 mL), and the combined organic layers were dried over sodium sulfate, filtered, concentrated under reduced pressure, and subjected to silica gel chromatography [Gradient: 0% to 100% (90:5:5 ethyl acetate/methanol/triethylamine) in heptane]. The product was obtained as a mixture with some impurities, and was used in the next step without additional purification. Yield: 270 mg, 0.723 mmol, 73%. APCI m/z 374.0 (M+1). 1H NMR (400 MHz, CD3OD), product peaks only: δ 2.25-2.34 (m, 2H), 3.8-4.0 (br m, 4H), 3.95 (s, 3H), 3.96 (s, 3H), 7.61 (br d, J=8.2 Hz, 2H), 7.76 (s, 1H), 7.92 (br d, J=8.4 Hz, 2H), 8.16 (s, 1H), 9.97 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with water
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe product was obtained as a mixture with some impurities
  8. customwas used in the next step without additional purification

Sources & evidence

ORD record
ord-78d5c09a39b449ec928ef932cb3f145c
Source dataset
uspto-grants-2014_09
Patent number
US08829010B2

Reaction notes

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