Diisopropylethylamine → tert-Butyl 4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-1-carboxylate

HRID 1192436Notes

Reaction equation

HRID 1192436 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(C(C)C)CC)(C)C.C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.C(OCC)(=O)C>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:2]2[N:7]=[CH:6][N:5]=[C:4]3[NH:8][N:9]=[CH:10][C:3]=23)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidineHCID 516892Sodium Bicarbonate

Product 1

HCID 11472214tert-Butyl 4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-1-carboxylateYield 84%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

The 4-chloro-1H-pyrazolo[3,4-d]pyrimidine (500 mg, 3.24 mmol) and piperazine-1-carboxylic acid tert-butyl ester (603 mg, 3.24 mmol) were dissolved in 11.0 mL of NMP then treated with diisopropylethyl amine (845 μL, 4.85 mmol). The yellow solution was heated to 80 C overnight to completion and was allowed to cool to room temperature. The solution was diluted with ethyl acetate, poured into diluted NaHCO3 solution, and extracted with ethyl acetate. The combined organic was washed with water, brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the crude material as a tan solid. The material was triturated with DCM/hexanes to afford the 4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester as a cream-colored solid (824 mg, 84%). 1H NMR (CDCl3, 400 MHz) δ 8.48 (s, 1H), 8.06 (s, 1H), 4.05 (m, 4H), 3.67 (m, 4H). LCMS (APCI+) m/z 305 [M+H]+; Rt=2.14 min.

Workup

  1. temperatureThe yellow solution was heated to 80 C overnight to completion
  2. extractionextracted with ethyl acetate
  3. washThe combined organic was washed with water, brine
  4. customseparated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford the crude material as a tan solid
  9. customThe material was triturated with DCM/hexanes

Sources & evidence

ORD record
ord-b7fcfa6d1b644650a45a29873b062f1d
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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