Triethylamine → 4-(4-Chloro-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylic acid isopropyl ester

HRID 1931591Notes

Reaction equation

HRID 1931591 reaction equation
C(N(CC)CC)C.Cl.[CH:9]([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].[Cl:23][C:24]1[C:29]([C:30](=O)[CH3:31])=[C:28](Cl)[N:27]=[CH:26][N:25]=1>C1(C)C=CC=CC=1>[CH:9]([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[C:30]([CH3:31])=[N:22]2)[CH2:19][CH2:20]1)=[O:14])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 122782591-(4,6-Dichloro-5-pyrimidinyl)ethanone2×HCID 669152794-Hydrazino-piperidine-1-carboxylic acid isopropyl ester hydrochloride2×

Product 1

HCID 579649474-(4-Chloro-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylic acid isopropyl esterYield 33.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Triethylamine (0.33 mL, 2.4 mmol) was added to a stirred mixture of 4-hydrazino-piperidine-1-carboxylic acid isopropyl ester hydrochloride (Intermediate 10; 188 mg, 0.8 mmol) and 1-(4,6-dichloro-pyrimidin-5-yl)-ethanone (Intermediate 17; 150 mg, 0.8 mmol) in toluene (5 mL) at room temperature under nitrogen and the resulting mixture was heated to reflux for 8 hours. The solvent was removed in vacuo and the crude reaction mixture was purified on a flash silica column (30 mm×4″) eluting with 10-33% ethyl acetate/hexanes to give 4-(4-chloro-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid isopropyl ester (90 mg, 33%). 1H NMR (300 MHz, DMSO-d6) δ 1.19 (d, 6H, J=6.3 Hz), 1.86-1.99 (m, 4H), 2.63 (s, 3H), 2.94-3.10 (m, 2H), 4.04-4.15 (m, 1H), 4.74-4.82 (m, 1H), 4.91-4.98 (m, 1H), 8.77 (s, 1H).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 8 hours
  3. customThe solvent was removed in vacuo
  4. customthe crude reaction mixture
  5. customwas purified on a flash silica column (30 mm×4″)
  6. washeluting with 10-33% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-e9ea6f5e2ecb43388ae00ab11ca5e388
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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