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

HRID 1711928Notes

Reaction equation

HRID 1711928 reaction equation
[CH3:1][NH:2][CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[N:11]([CH3:13])[CH:10]=[CH:9]2.Cl.Cl.[CH3:16][N:17]1[CH2:23][C:22]2[CH:24]=[C:25](/[CH:28]=[CH:29]/[C:30](O)=[O:31])[CH:26]=[N:27][C:21]=2[NH:20][C:19](=[O:33])[CH2:18]1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[CH3:1][N:2]([CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[N:11]([CH3:13])[CH:10]=[CH:9]2)[C:30](=[O:31])/[CH:29]=[CH:28]/[C:25]1[CH:26]=[N:27][C:21]2[NH:20][C:19](=[O:33])[CH2:18][N:17]([CH3:16])[CH2:23][C:22]=2[CH:24]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 33589520N-Methyl-1-(1-methyl-1H-indol-7-yl)methanamineHCID 66967454(E)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid dihydrochloride

Product 1

HCID 66966535(E)-N-methyl-N-(1-methylindol-7-ylmethyl)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamideYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (methyl-(1-methyl-1H-indol-7-ylmethyl)amine (103 mg, 0.6 mmol), (E)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid dihydrochloride (160 mg, 0.5 mmol), HOBt (81 mg, 0.5 mmol) and diisopropylethylamine (0.41 mL, 2 mmol) in DMF (12 mL) was added EDC hydrochloride (114 mg, 0.6 mmol). The mixture was stirred overnight at room temperature. Water (75 mL) was added and the solution stirred for 1 hr. The precipitate was collected by filtration and triturated with hexanes to afford (E)-N-methyl-N-(1-methylindol-7-ylmethyl)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide (100 mg, 50%) as a white solid and as a mixture of amide rotomers. 1H NMR (300 MHz, DMSO-d6) δ 10.33 (m, 1H), 8.54-8.47 (m, 1H), 8.16-7.97 (m, 1H), 7.62-7.19 (m, 4H), 6.92-6.97 (m, 1H), 6.78-6.58 (m, 1H), 6.39 (d, J=3.1 Hz, 1H) 5.48-5.19 (2×s, 2H), 3.99-4.11 (2×s, 3H), 3.79-3.70 (2×s, 2H), 3.42-3.36 (m, 2H), 3.30-3.13 (2×s, 3H), 2.36-2.30 (2×s, 3H); ESI MS m/z 404 [C23H25N5O2+H]+.

Workup

  1. stirringthe solution stirred for 1 hr
  2. filtrationThe precipitate was collected by filtration
  3. customtriturated with hexanes

Sources & evidence

ORD record
ord-31de69b281304161bdba3de3f11cf3e4
Source dataset
uspto-grants-2010_09
Patent number
US07790709B2

Reaction notes

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