Triphenylphosphine → 3-bromo-4-chloro-1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidine

HRID 897440Notes

Reaction equation

HRID 897440 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[Cl:11])[NH:4][N:3]=1.[O:12]1[C:16]2([CH2:21][CH2:20][CH:19](O)[CH2:18][CH2:17]2)[O:15][CH2:14][CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[Cl:11])[N:4]([CH:19]2[CH2:20][CH2:21][C:16]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:17][CH2:18]2)[N:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5673521,4-Dioxaspiro(4.5)decan-8-ol2×HCID 5462977Diethyl azodicarboxylateHCID 1784783943-Bromo-4-chloro-1H-pyrazolo[3,4-d]pyrimidine2×

Product 1

HCID 223470503-bromo-4-chloro-1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidineYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 3-bromo-4-chloropyrazolo[3,4-d]pyrimidine (Intermediate B) (7.5 g, 32 mmol), 1,4-dioxaspiro[4.5]decan-8-ol (Intermediate M) (15.17 g, 96 mmol), triphenylphosphine (16.86 g, 64 mmol) in THF (275 mL) was added diethylazodicarboxylate (11.14 g, 64 mmol) in THF (50 mL) at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 1 hour, warmed to room temperature and then stirred at room temperature for 3 hrs. The reaction mixtures was concentrated in vacuo and dissolved in hot heptane/EtOAc/DCM (5:1:5). Flash silica gel column chromatography using heptane, heptane/EtOAc (5/1) then heptane/EtOAc (4/1) gave a solid which was triturated with heptane and the solids removed by filtration to furnish 8.2 g of 3-bromo-4-chloro-1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidine as a white solid (69%) [Rf in 1:1 heptane:EtOAc=0.5]1H NMR (400 MHz, d6-DMSO): 8.89 (1H, s), 4.92 (1H, m), 3.90 (4H, m), 2.16 (2H, m), 1.96 (2H, m), 1.81 (6H, m) HPLC: Tr=17.11 mins, 96.6%

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred at room temperature for 3 hrs
  3. customThe reaction mixtures
  4. concentrationwas concentrated in vacuo
  5. dissolutiondissolved in hot heptane/EtOAc/DCM (5:1:5)
  6. customheptane/EtOAc (4/1) gave a solid which
  7. customwas triturated with heptane
  8. customthe solids removed by filtration

Sources & evidence

ORD record
ord-c965cf36ad79485593e0a3052962f8b7
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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