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

HRID 1931587Notes

Reaction equation

HRID 1931587 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([NH:21][NH2:22])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].[Cl:23][C:24]1[C:29]([CH:30]=O)=[C:28](Cl)[N:27]=[CH:26][N:25]=1>C1(C)C=CC=CC=1>[C:8]([O:12][C:13]([N:15]1[CH2:16][CH2:17][CH:18]([N:21]2[C:28]3=[N:27][CH:26]=[N:25][C:24]([Cl:23])=[C:29]3[CH:30]=[N:22]2)[CH2:19][CH2:20]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 8196914,6-Dichloro-5-pyrimidinecarbaldehyde2×HCID 56965816HCID 56965816, compound2×

Product 1

HCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylateYield 34%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Triethylamine (19.5 mL, 140 mmol) was added to a stirred solution of 4-hydrazino-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 9; 15.0 g, 69.7 mmol) and 4,6-dichloro-pyrimidine-5-carbaldehyde (Intermediate 16; 12.34 g, 69.7 mmol) in toluene (100 mL) at room temperature under nitrogen and the resulting mixture was heated to reflux for 6 hours. The solvent was removed in vacuo and the crude reaction mixture was purified by column chromatography (silica gel, 100-200 mesh; 5% ethyl acetate/hexanes) to give 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (8.0 g, 34%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 1.97-2.00 (m, 2H), 2.19-2.29 (m, 2H), 2.90-3.00 (br s, 2H), 4.25-4.35 (m, 2H), 4.92-5.00 (m, 1H), 8.15 (s, 1H), 8.74 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 28.3, 31.1, 42.8, 55.3, 79.8, 113.8, 131.8, 152.4, 154.1, 154.4, 154.7. HRMS Calcd. for C15H21ClN5O2 (MH+): 338.1379. Found: 338.1377.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 6 hours
  3. customThe solvent was removed in vacuo
  4. customthe crude reaction mixture
  5. customwas purified by column chromatography (silica gel, 100-200 mesh; 5% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bb4edfcb70b24b32a6ef4c57f4280bc9
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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