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

HRID 1094225Notes

Reaction equation

HRID 1094225 reaction equation
Cl[C:2]1[C:7]([O:8][CH3:9])=[C:6]([Cl:10])[N:5]=[C:4]([CH3:11])[N:3]=1.C(N(C(C)C)CC)(C)C.[NH:21]1[CH2:26][CH2:25][CH:24]([C:27]2[CH:36]=[CH:35][C:34]3[C:29](=[N:30][CH:31]=[CH:32][CH:33]=3)[N:28]=2)[CH2:23][CH2:22]1.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.CC(N(C)C)=O>[Cl:10][C:6]1[N:5]=[C:4]([CH3:11])[N:3]=[C:2]([N:21]2[CH2:22][CH2:23][CH:24]([C:27]3[CH:36]=[CH:35][C:34]4[C:29](=[N:30][CH:31]=[CH:32][CH:33]=4)[N:28]=3)[CH2:25][CH2:26]2)[C:7]=1[O:8][CH3:9]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 582936514,6-dichloro-5-methoxy-2-methylPyrimidineHCID 666409192-(Piperidin-4-YL)-1,8-naphthyridine

Product 1

HCID 866189262-[1-(6-Chloro-5-methoxy-2-methyl-pyrimidin-4-yl)-piperidin-4-yl]-[1,8]naphthyridineYield 50.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

30 ml of dimethylacetamide, 0.9 g (4.66 mmoles) 4,6-dichloro-2-methyl-5-methoxy-pyrimidine and 3 ml of diisopropylethylamine are added into a single-necked flask containing 1.1 g (5.2 mmoles) of 2-piperidin-4-yl-[1,8]naphthyridine. This mixture is heated at 120° C. for 4 hours then concentrated to dryness under reduced pressure (2 kPa). 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 of 100-0 to 0-100. 870 mg of expected product is obtained in the form of a yellow solid.

Workup

  1. concentrationthen concentrated to dryness under reduced pressure (2 kPa)
  2. customThe residue obtained
  3. customThe organic phase is separated
  4. dry with materialThe collected organic phases are dried over magnesium sulphate
  5. customthe solvent is evaporated off under reduced pressure (2 kPa)
  6. customThe residue is chromatographed on silica gel eluting with a gradient of heptane-ethyl acetate of 100-0 to 0-100

Sources & evidence

ORD record
ord-183924e31bd74b5794c6554e38b0bf6f
Source dataset
uspto-grants-2012_03
Patent number
US08133896B2

Reaction notes

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