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

HRID 1615957Notes

Reaction equation

HRID 1615957 reaction equation
C(N(C(C)C)CC)(C)C.[C:10]([C:14]1[N:19]=[C:18]([Cl:20])[C:17]([CH3:21])=[C:16](Cl)[N:15]=1)([CH3:13])([CH3:12])[CH3:11].[NH:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:38]=[CH:37][C:36]3[C:31](=[N:32][CH:33]=[CH:34][CH:35]=3)[N:30]=2)[CH2:25][CH2:24]1.N1C2C(=CC=CN=2)C=CC=1.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.CC(N(C)C)=O>[C:10]([C:14]1[N:15]=[C:16]([N:23]2[CH2:24][CH2:25][CH:26]([C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[N:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)[CH2:27][CH2:28]2)[C:17]([CH3:21])=[C:18]([Cl:20])[N:19]=1)([CH3:11])([CH3:12])[CH3:13]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 1360691,8-NaphthyridineHCID 516892Sodium BicarbonateHCID 8246602-Tert-butyl-4,6-dichloro-5-methylpyrimidineHCID 666409192-(Piperidin-4-YL)-1,8-naphthyridine

Product 1

HCID 866189282-[1-(2-Tert-butyl-6-chloro-5-methyl-pyrimidin-4-yl)-piperidin-4-yl]-[1,8]naphthyridineYield 65.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

20 ml of dimethylacetamide and 5 ml (17.8 mmoles) of diisopropylethylamine are added into a single-necked flask containing 1.5 g (6.84 mmoles) of 2-tert-butyl-4,6-dichloro-5-methyl-pyrimidine and 1.46 g (6.84 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 mixture is heated for another 6 hours. The reaction mixture is returned to ambient temperature before concentrating 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 (70-30) to heptane-ethyl acetate (50-50). 1.77 g of expected product is obtained.

Workup

  1. temperaturethe mixture is heated for another 6 hours
  2. customis returned to ambient temperature
  3. concentrationbefore concentrating to dryness
  4. customThe residue obtained
  5. customThe organic phase is separated
  6. dry with materialThe collected organic phases are dried over magnesium sulphate
  7. customthe solvent is evaporated off under reduced pressure (2 kPa)
  8. customThe residue is chromatographed on silica gel eluting with a gradient of heptane-ethyl acetate (70-30) to heptane-ethyl acetate (50-50)

Sources & evidence

ORD record
ord-2d4ee827e48c45ca8a11ef61371bbe56
Source dataset
uspto-grants-2014_07
Patent number
US08765766B2

Reaction notes

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