Diisopropylethylamine → (E)-N-(3-Isopropyl-2-propoxybenzyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-(1,8]naphthyridin-3-yl)acrylamide

HRID 1362285Notes

Reaction equation

HRID 1362285 reaction equation
[CH:1]([C:4]1[C:5]([O:13][CH2:14][CH2:15][CH3:16])=[C:6]([CH:10]=[CH:11][CH:12]=1)[CH2:7]CN)([CH3:3])[CH3:2].[CH:17]([N:20](C(C)C)CC)(C)C.Cl.[O:27]=[C:28]1[NH:37][C:36]2[N:35]=[CH:34][C:33](/[CH:38]=[CH:39]/[C:40]([OH:42])=O)=[CH:32][C:31]=2[CH2:30][CH2:29]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O>[CH:1]([C:4]1[C:5]([O:13][CH2:14][CH2:15][CH3:16])=[C:6]([CH:10]=[CH:11][CH:12]=1)[CH2:7][N:20]([CH3:17])[C:40](=[O:42])/[CH:39]=[CH:38]/[C:33]1[CH:34]=[N:35][C:36]2[NH:37][C:28](=[O:27])[CH2:29][CH2:30][C:31]=2[CH:32]=1)([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid HydrochlorideHCID 66966658(3-Isopropyl-2-propoxybenzyl)methylamine

Product 1

HCID 16662051(E)-N-(3-Isopropyl-2-propoxybenzyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-(1,8]naphthyridin-3-yl)acrylamideYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (3-isopropyl-2-propoxybenzyl)methylamine (0.238 g, 1.07 mmol) and diisopropyl-ethylamine (0.51 mL, 2.9 mmol) in DMF (20 mL) under N2 was treated sequentially with (E)-3-(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)acrylic acid hydrochloride (0.250 g, 0.981 mmol), 1-hydroxybenzotriazole hydrate (0.144 g, 1.07 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.205 g, 1.07 mmol). After stirring for 18 h, the reaction mixture was diluted with H2O (30 mL). The resulting solids were collected by filtration and when washed with Et2O (50 mL) were unexpectedly dissolved. The filtrate was extracted with EtOAc (3×50 mL). The combined organics were washed with brine (2×100 mL), dried (Na2SO4) and concentrated to a light yellow solid. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 99.5:0.5) gave the title compound (0.26 g, 63%) as a white solid and as a mixture of amide rotamers: 1H NMR (500 MHz, DMSO-d6) δ 10.64-10.62 (m, 1H), 8.37-8.31 (m, 1H), 8.09-7.98 (m, 1H), 7.52-7.49 (m, 1H), 7.28-7.19 (m, 2H), 7.10-7.06 (m, 1H), 6.89-6.87 (m, 1H), 4.80-4.66 (m, 2H), 3.76-3.70 (m, 2H), 3.31-3.26 (m, 1H), 3.12-2.85 (m, 5H), 2.55-2.49 (m, 2H), 1.82-1.76 (m, 2H), 1.19-1.17 (m, 6H), 1.05-1.02 (m, 3H); MS (ESI) m/e 422 (M+H)+.

Workup

  1. filtrationThe resulting solids were collected by filtration and when
  2. washwashed with Et2O (50 mL)
  3. dissolutionwere unexpectedly dissolved
  4. extractionThe filtrate was extracted with EtOAc (3×50 mL)
  5. washThe combined organics were washed with brine (2×100 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to a light yellow solid
  8. customPurification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 99.5:0.5)

Sources & evidence

ORD record
ord-6bb9a41a7c6644919ea0f56ef1c3356a
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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