Triphenylphosphine → Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate

HRID 604991Notes

Reaction equation

HRID 604991 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.O[CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[N:9]=[CH:10][C:3]=12

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a flame dried round bottom flask under N2 was added 4-chloropyrazolo[3,4-d]pyrimidine (J. Am. Chem. Soc. 1956, 78, 784) (1.80 g, 11.65 mmol), t-butyl 4-hydroxy-1-piperidinecarboxylate (2.46 g, 12.23 mol), and PS—PPh3 (9.21 g, 1.77 mmol/g) in anhydrous tetrahydrofuran (200 mL). The mixture was cooled to 0° C. and diethyl azodicarboxylate (DEAD) (2.20 mL, 13.98 mmol) in tetrahydrofuran (20 mL) was added dropwise. The mixture was allowed to warm to room temperature and stirred overnight. The reaction was then filtered and taken up in methylene chloride. The insoluble material was filtered off. The filtrate was concentrated, taken up in methylene chloride, and put in the freezer for 5 hr. The crystals that formed were filtered off and the filtrate was purified by silica gel chromatography (0-2% methanol/methylene chloride) to give pure tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate. 1H-NMR (500 MHz, CDCl3) δ 8.76 (s, 1H), 8.16 (s, 1H), 4.92-5.02 (m, 1H), 4.32 (br s, 2H), 2.97 (br s, 2H), 2.20-2.31 (m, 2H), 1.96-2.05 (m, 2H). LRMS m/z (M+H) Calcd: 337.13, found: 338.09.

Workup

  1. customTo a flame dried round bottom flask under N2
  2. temperatureto warm to room temperature
  3. filtrationThe reaction was then filtered
  4. filtrationThe insoluble material was filtered off
  5. concentrationThe filtrate was concentrated
  6. waitput in the freezer for 5 hr
  7. customThe crystals that formed
  8. filtrationwere filtered off
  9. customthe filtrate was purified by silica gel chromatography (0-2% methanol/methylene chloride)

Sources & evidence

ORD record
ord-54821f90a3f4456492b7fe40d7672f92
Source dataset
uspto-grants-2011_03
Patent number
US07910561B2

Reaction notes

Loading…