Diisopropylethylamine → HCID 86618547, compound

HRID 2242976Notes

Reaction equation

HRID 2242976 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([NH2:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].C(N(C(C)C)C(C)C)C>C(#N)C>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([NH:23][C:6]2[C:5]([F:9])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 86618547HCID 86618547, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2,4-dichloro-5-fluoro-pyrimidine (1.28 g, 7.68 mmol, 1.0 equiv; commercially available), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.0 g, 10.0 mmol, 1.3 equiv) and N-ethyl diisopropylamine (3.0 mL, 2.3 g, 17.7 mmol, 2.3 equiv) in acetonitrile (16 mL) was heated by microwave irradiation to 160° C. for 20 min. The reaction mixture was concentrated under reduced pressure and the crude material purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 2.23 g (88%) of the title compound. 1H NMR (400 MHz, DMSO): δ 1.38-1.48 (m, 2H), 1.41 (s, 9H), 1.78-1.82 (m, 2H), 2.84 (br s, 2H), 3.93-3.96 (m, 2H), 4.00-4.08 (m, 1H), 8.02 (d, J=6.0 Hz, 1H), 8.09 (d, J=4.0 Hz, 1H). 13C NMR (100 MHz, DMSO): δ 28.06, 30.75, 43.33, 47.34, 78.66, 139.86 (d, J=20.3 Hz), 145.03 (d, J=255.7 Hz), 152.63 (d, J=13.4 Hz), 153.49 (d, J=2.7 Hz), 153.83. MS (ISP): 331.3 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe crude material purified by silica column chromatography
  3. washeluting with a gradient of heptane/ethyl acetate providing 2.23 g (88%) of the title compound

Sources & evidence

ORD record
ord-7c83f7734a89486d906056e842430b18
Source dataset
uspto-grants-2010_03
Patent number
US07674804B2

Reaction notes

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