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

HRID 1362271Notes

Reaction equation

HRID 1362271 reaction equation
[Cl:1][C:2]1[C:3]([O:11][CH:12]([CH3:14])C)=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5]CN.[CH:15]([N:18](C(C)C)CC)(C)C.Cl.[O:25]=[C:26]1[NH:35][C:34]2[N:33]=[CH:32][C:31](/[CH:36]=[CH:37]/[C:38]([OH:40])=O)=[CH:30][C:29]=2[CH2:28][CH2:27]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O>[Cl:1][C:2]1[C:3]([O:11][CH2:12][CH3:14])=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][N:18]([CH3:15])[C:38](=[O:40])/[CH:37]=[CH:36]/[C:31]1[CH:32]=[N:33][C:34]2[NH:35][C:26](=[O:25])[CH2:27][CH2:28][C:29]=2[CH:30]=1

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 66967106(3-Chloro-2-isopropoxybenzyl)methylamine

Product 1

HCID 16662047(E)-N-(3-Chloro-2-ethoxybenzyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)acrylamideYield 21.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A stirring solution of (3-chloro-2-isopropoxybenzyl)methylamine (0.229 g, 1.07 mmol) and diisopropylethylamine (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, 0.980 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 washed with Et2O (100 mL), suspended in MeOH (30 mL) and sonicated for 30 minutes. The solids were then collected by filtration, washed with MeOH and dried to yield the title compound (0.085 g, 21%) as a white solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.67-10.64 (m, 1H), 8.37-8.32 (m, 1H), 8.09-7.91 (m, 1H), 7.53-7.48 (m, 1H), 7.42-7.37 (m, 1H), 7.28-7.02 (m, 3H), 4.83-4.68 (m, 2H), 4.53-4.45 (m, 1H), 2.94-2.85 (m, 5H), 2.56-2.49 (m, 2H), 1.33-1.28 (m, 6H); MS (ESI) m/e 414 (M+H)+.

Workup

  1. filtrationThe resulting solids were collected by filtration
  2. washwashed with Et2O (100 mL)
  3. customsonicated for 30 minutes
  4. filtrationThe solids were then collected by filtration
  5. washwashed with MeOH
  6. customdried

Sources & evidence

ORD record
ord-2927bddf6f0648a682c36983a9ae0f4f
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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