Diisopropylethylamine → (E)-N-Methyl-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-N-(1-propyl-naphthalen-2-ylmethyl)acrylamide

HRID 1362158Notes

Reaction equation

HRID 1362158 reaction equation
Cl.[CH3:2][N:3]1[CH2:9][C:8]2[CH:10]=[C:11](/[CH:14]=[CH:15]/[C:16]([OH:18])=O)[CH:12]=[N:13][C:7]=2[NH:6][C:5](=[O:19])[CH2:4]1.[CH3:20][NH:21][CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]=1[CH2:33][CH2:34][CH3:35].C(N(C(C)C)CC)(C)C.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[CH3:20][N:21]([CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]=1[CH2:33][CH2:34][CH3:35])[C:16](=[O:18])/[CH:15]=[CH:14]/[C:11]1[CH:12]=[N:13][C:7]2[NH:6][C:5](=[O:19])[CH2:4][N:3]([CH3:2])[CH2:9][C:8]=2[CH:10]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 59456959Methyl-(1-propyl-naphthalen-2-ylmethyl)amineHCID 66966197(E)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochloride

Product 1

HCID 9956756(E)-N-Methyl-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-N-(1-propyl-naphthalen-2-ylmethyl)acrylamideYield 41.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(E)-3-(4-Methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochloride (1.40 g, 1.25 mmol) was added to a solution of methyl-(1-propyl-naphthalen-2-ylmethyl)amine (0.292 g, 1.37 mmol) and diisopropylethylamine (0.65 mL, 3.75 mmol) in DMF (25 mL) followed by the addition of 1-hydroxybenzotriazole hydrate (0.185 g, 1.37 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.263 g, 1.37 mmol). The reaction was allowed to stir at room temperature for 18 h. The reaction was quenched with H2O (70 mL) then concentrated to a yellow oil. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 99:1 to 95:5) gave the title compound (0.229 g, 41%) as a glassy orange solid and as a mixture of amide rotamers: 1H NMR (500 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.55-8.54 (m, 1H), 8.24-8.14 (m, 1H), 7.98-7.86 (m, 5H), 7.72-7.24 (m, 3H), 3.75 (s, 2H), 3.42 (s, 2H), 3.86 (s, 2H), 2.54-2.36 (m, 6H), 2.11-2.02 (m, 2H), 1.40-1.34 (m, 2H), 1.01-0.98 (m, 3H).

Workup

  1. customThe reaction was quenched with H2O (70 mL)
  2. concentrationthen concentrated to a yellow oil
  3. customPurification by column chromatography (silica gel, CH2Cl2/MeOH, 99:1 to 95:5)

Sources & evidence

ORD record
ord-9e087a7056334c29b402666bf83068ac
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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