Diisopropylethylamine → (E)-N-(1H-indol-6-ylmethyl)-N-methyl-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide

HRID 1362250Notes

Reaction equation

HRID 1362250 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:10][NH:11][CH3:12])[CH:8]=2)[CH:3]=[CH:2]1.Cl.Cl.[CH3:15][N:16]1[CH2:22][C:21]2[CH:23]=[C:24](/[CH:27]=[CH:28]/[C:29]([OH:31])=O)[CH:25]=[N:26][C:20]=2[NH:19][C:18](=[O:32])[CH2:17]1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:10][N:11]([CH3:12])[C:29](=[O:31])/[CH:28]=[CH:27]/[C:24]3[CH:25]=[N:26][C:20]4[NH:19][C:18](=[O:32])[CH2:17][N:16]([CH3:15])[CH2:22][C:21]=4[CH:23]=3)[CH:8]=2)[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 33754749((1H-indol-6-yl)methyl)(methyl)amineHCID 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 10091733(E)-N-(1H-indol-6-ylmethyl)-N-methyl-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamideYield 45.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (1H-indol-6-ylmethyl)methylamine (98 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-(1H-indol-6-ylmethyl)-N-methyl-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide (89 mg, 37%) as a white solid and as a mixture of amide rotomers. 1H NMR (300 MHz, DMSO-d6) δ 11.03-11.01 (m, 1H), 10.33-10.30 (m, 1H), 8.52 (d, J=7.6 Hz, 1H), 8.13 (d, J=2.4 Hz, 1H), 7.60-7.22 (m, 5H), 6.92-6.86 (m, 1H), 6.37 (s, 1H), 4.88-4.68 (2×s, 2H), 3.78-3.74 (m, 2H), 3.42-3.38 (m, 2H), 3.08-2.89 (2×s, 3H), 2.36-2.33 (2×s, 3H); ESI MS m/z 390 [C22H23N5O2+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-cdd0cd89eb284b2dba5668e33d88e1bc
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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