Diisopropylethylamine → 2-[1-(2-Cyclopropyl-6-chloro-5-methyl-pyrimidin-4-yl)-piperidin-4-yl]-[1,8]naphthyridine

HRID 1094230Notes

Reaction equation

HRID 1094230 reaction equation
C(N(C(C)C)CC)(C)C.[CH:10]1([C:13]2[N:18]=[C:17]([Cl:19])[C:16]([CH3:20])=[C:15](Cl)[N:14]=2)[CH2:12][CH2:11]1.[NH:22]1[CH2:27][CH2:26][CH:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[N:31][CH:32]=[CH:33][CH:34]=3)[N:29]=2)[CH2:24][CH2:23]1.N1C2C(=CC=CN=2)C=CC=1.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.CC(N(C)C)=O>[CH:10]1([C:13]2[N:14]=[C:15]([N:22]3[CH2:23][CH2:24][CH:25]([C:28]4[CH:37]=[CH:36][C:35]5[C:30](=[N:31][CH:32]=[CH:33][CH:34]=5)[N:29]=4)[CH2:26][CH2:27]3)[C:16]([CH3:20])=[C:17]([Cl:19])[N:18]=2)[CH2:11][CH2:12]1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 1360691,8-NaphthyridineHCID 516892Sodium BicarbonateHCID 545957314,6-Dichloro-2-cyclopropyl-5-methylpyrimidineHCID 666409192-(Piperidin-4-YL)-1,8-naphthyridine

Product 1

HCID 866189292-[1-(2-Cyclopropyl-6-chloro-5-methyl-pyrimidin-4-yl)-piperidin-4-yl]-[1,8]naphthyridineYield 51.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

20 ml of dimethylacetamide and 3.36 ml (19.2 mmoles) of diisopropylethylamine are added into a single-necked flask containing 1.5 g (7.39 mmoles) of 2-cyclopropyl-4,6-dichloro-5-methyl-pyrimidine and 1.58 g (7.39 mmoles) of 2-piperidin-4-yl-[1,8]naphthyridine. This mixture is heated at 100° C. overnight. The next day 0.2 equivalent of naphthyridine is added and the reaction mixture is heated for another 6 hours, followed by returning to ambient temperature before concentration to dryness. The residue obtained is taken up in a mixture of water, ethyl acetate and a saturated solution of sodium bicarbonate. The organic phase is separated and the aqueous phase reextracted with ethyl acetate. The collected organic phases are dried over magnesium sulphate then the solvent is evaporated off under reduced pressure (2 kPa). The residue is chromatographed on silica gel eluting with a gradient of heptane-ethyl acetate (50-50) to 100% ethyl acetate. 1.45 g of expected product is obtained.

Workup

  1. temperaturethe reaction mixture is heated for another 6 hours
  2. concentrationby returning to ambient temperature before concentration to dryness
  3. customThe residue obtained
  4. customThe organic phase is separated
  5. dry with materialThe collected organic phases are dried over magnesium sulphate
  6. customthe solvent is evaporated off under reduced pressure (2 kPa)
  7. customThe residue is chromatographed on silica gel eluting with a gradient of heptane-ethyl acetate (50-50) to 100% ethyl acetate

Sources & evidence

ORD record
ord-64013a6b865a4078997bd59c9f044f8b
Source dataset
uspto-grants-2012_03
Patent number
US08133896B2

Reaction notes

Loading…