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

HRID 2261158Notes

Reaction equation

HRID 2261158 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-1e89b9f0bede49d6b6799b13468f626e
Source dataset
uspto-grants-2010_12
Patent number
US07846932B2

Reaction notes

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