Piperidine → HCID 67269263, compound

HRID 600221Notes

Reaction equation

HRID 600221 reaction equation
C(O[C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH3:21])[CH2:16][CH2:15]2)[N:11]=[CH:10][N:9]=1)(C)(C)C.C[Al](C)C.[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>C1(C)C=CC=CC=1>[CH2:20]([N:17]1[CH2:16][CH2:15][N:14]([C:12]2[N:11]=[CH:10][N:9]=[C:8]([NH:7][C:6]([N:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:22])[CH:13]=2)[CH2:19][CH2:18]1)[CH3:21]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 16682925TrimethylaluminumHCID 67269573HCID 67269573, compound

Product 1

HCID 67269263HCID 67269263, compoundYield 18.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
120 °C

Procedure

A mixture of 1.6 g (7.75 mmol) 6-(4-ethyl-piperazin-1-yl)-pyrimidin-4-ylamine (intermediate 4), 2.03 g (9.3 mmol) di-tert-butyl dicarbonate and 1.17 g (11.6 mmol) NEt3 in 30 mL DCM was stirred at 50° C. in a sealed tube for 16 h. After evaporation of all volatiles the residue was purified with flash column chromatography on silica. The combined product fractions were evaporated to dryness to yield [6-(4-ethyl-piperazin-1-yl)-pyrimidin-4-yl]-carbamic acid tert-butyl ester. MS(m/e): 308.4 (MH+). A mixture of 28 mg (0.09 mmol) [6-(4-ethyl-piperazin-1-yl)-pyrimidin-4-yl]-carbamic acid tert-butyl ester, 0.18 mL (0.36 mmol) 2M AlMe3 solution in toluene and 30 mg (0.36 mmol) piperidine in 1 mL toluene were heated to 120° C. for 16 h. After removal of all volatiles under reduced pressure the residue was taken up in methanol/NEt3 and subjected to preparative HPLC purification on reversed phase eluting with a gradient of acetonitrile/water (0.05% triethylamine). The combined product fractions were evaporated to dryness to yield 5.3 mg (18%) of the title compound. MS (m/e): 319.1 (MH+).

Workup

  1. customAfter removal of all volatiles under reduced pressure the residue
  2. customsubjected to preparative HPLC purification on reversed phase
  3. washeluting with a gradient of acetonitrile/water (0.05% triethylamine)
  4. customThe combined product fractions were evaporated to dryness

Sources & evidence

ORD record
ord-a19f27184e24482aa94b406bd5e8630c
Source dataset
uspto-grants-2011_03
Patent number
US07902184B2

Reaction notes

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