Diisopropylethylamine → (R)-(E)-N-Methyl-N-(3-methylbenzofuran-2-ylmethyl)-3-(10-oxo-2,3,4,9,10,10a-hexahydro-1H-3a,8,9-triazabenzo[f]azulen-6-yl)acrylamide

HRID 2097043Notes

Reaction equation

HRID 2097043 reaction equation
[CH3:1][NH:2][CH2:3][C:4]1[O:5][C:6]2[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=2[C:8]=1[CH3:9].[CH:14](N(C(C)C)CC)([CH3:16])[CH3:15].Br[C:24]1[CH:25]=[N:26][C:27]2[NH:36][C:35](=[O:37])[C@@H:34]3[N:30]([CH2:31][CH2:32][CH2:33]3)[CH2:29][C:28]=2[CH:38]=1.O.[OH:40]N1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O>[CH3:1][N:2]([CH2:3][C:4]1[O:5][C:6]2[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=2[C:8]=1[CH3:9])[C:15](=[O:40])/[CH:14]=[CH:16]/[C:24]1[CH:25]=[N:26][C:27]2[NH:36][C:35](=[O:37])[C@@H:34]3[N:30]([CH2:31][CH2:32][CH2:33]3)[CH2:29][C:28]=2[CH:38]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 46785639N-methyl-1-(3-methylbenzofuran-2-yl)methanamineHCID 59456939(R)-6-bromo-1,2,3,4,9,10a-hexahydro-3a,8,9-triazabenzo[f]azulen-10-one

Product 1

HCID 16659662(R)-(E)-N-Methyl-N-(3-methylbenzofuran-2-ylmethyl)-3-(10-oxo-2,3,4,9,10,10a-hexahydro-1H-3a,8,9-triazabenzo[f]azulen-6-yl)acrylamideYield 249.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of methyl-(3-methylbenzofuran-2-ylmethyl)amine (0.166 g, 0.953 mmol) and diisopropylethylamine (0.45 mL, 2.59 mmol) in DMF (20 mL) under N2 was treated sequentially with (R)-6-bromo-1,2,3,4,9,10a-hexahydro-3a,8,9-triazabenzo[f]azulen-10-one (0.300 g, 0.866 mmol), 1-hydroxybenzotriazole hydrate (0.128 g, 0.953 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.182 g, 0.953 mmol). After stirring for 18 h, the reaction mixture was diluted with H2O (30 mL). The resulting solids were collected by filtration, washed with Et2O and dried to give the title compound (0.93 g, 31%) as a white solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.38 (s, 1H), 8.59-8.56 (m, 1H), 8.23-8.21 (m, 1H), 7.58-7.21 (m, 6H), 5.00-4.79 (m, 2H), 3.96-3.92 (m, 1H), 3.55-3.47 (m, 2H), 3.19-2.84 (m, 4H), 2.61-2.59 (m, 1H), 2.26 (m, 4H), 1.76-1.74 (m, 3H).

Workup

  1. filtrationThe resulting solids were collected by filtration
  2. washwashed with Et2O
  3. customdried

Sources & evidence

ORD record
ord-695d4487de9846dcae4db59bc50e68ab
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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