1-Hydroxybenzotriazole → (E)-N-acenaphthen-5-ylmethyl-3-(6-amino-pyridin-3-yl)-N-methyl-acrylamide hydrochloride

HRID 1711925Notes

Reaction equation

HRID 1711925 reaction equation
[CH2:1]1[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[C:6]([CH2:13][NH:14][CH3:15])=[CH:5][CH:4]=[C:3]3[CH2:2]1.[NH2:16][C:17]1[N:22]=[CH:21][C:20](/[CH:23]=[CH:24]/[C:25]([OH:27])=O)=[CH:19][CH:18]=1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.[ClH:58]>CN(C=O)C.O>[ClH:58].[CH2:1]1[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[C:6]([CH2:13][N:14]([CH3:15])[C:25](=[O:27])/[CH:24]=[CH:23]/[C:20]2[CH:21]=[N:22][C:17]([NH2:16])=[CH:18][CH:19]=2)=[CH:5][CH:4]=[C:3]3[CH2:2]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10487224(2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acidHCID 669671841-(1,2-Dihydroacenaphthylen-5-yl)-N-methylmethanamine

Product 1

HCID 66967476(E)-N-acenaphthen-5-ylmethyl-3-(6-amino-pyridin-3-yl)-N-methyl-acrylamide hydrochlorideYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of acenaphthen-5-ylmethyl-methylamine (216 mg, 1.1 mmol), (E)-3-(6-amino-pyridin-3-yl)acrylic acid (164 mg, 1 mmol), HOBt (148 mg, 1.1 mmol) and diisopropylethylamine (0.8 mL, 4.4 mmol) in DMF (20 mL) was added EDC hydrochloride (210 mg, 1.1 mmol). The mixture was stirred overnight at room temperature. Water (100 mL) was added and the solution stirred for 1 hour. The precipitate was collected by filtration. The yellow solid was preabsorded onto silica gel and purified by column chromatography (95:5 CH2Cl2/MeOH). The residue was dissolved into methylene chloride followed by addition of 1M HCl/ether. The precipitate was collected by filtration to afford (E)-N-acenaphthen-5-ylmethyl-3-(6-amino-pyridin-3-yl)-N-methyl-acrylamide hydrochloride (120 mg, 32%) as a white solid and as a mixture of amide rotomers. 1H NMR (300 MHz, DMSO-d6) δ 8.44-8.28 (m, 3H), 7.84-7.72 (m, 1H), 7.59-7.12 (m, 6H), 7.07-6.92 (m, 1H), 5.15-5.02 (2×s, 2H), 3.35-3.15 (bs, 2H), 3.18 (s, 4H), 3.07-2.90 (2×s, 3H); ESI MS m/z 344 [C22H21N3O+H]+.

Workup

  1. stirringthe solution stirred for 1 hour
  2. filtrationThe precipitate was collected by filtration
  3. custompurified by column chromatography (95:5 CH2Cl2/MeOH)
  4. dissolutionThe residue was dissolved into methylene chloride
  5. additionfollowed by addition of 1M HCl/ether
  6. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-2375ddccc24242379244ba9ac67481f5
Source dataset
uspto-grants-2010_09
Patent number
US07790709B2

Reaction notes

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