Diisopropylethylamine → HCID 136348421, compound

HRID 1748719Notes

Reaction equation

HRID 1748719 reaction equation
Cl.Cl.[CH3:3][N:4]1[C:8]2[NH:9][CH2:10][CH2:11][S:12][CH:13]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[C:7]=2[C:6]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)=[N:5]1.[CH3:26][C:27]1[C:32]([C:33](O)=[O:34])=[CH:31][CH:30]=[CH:29][N:28]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH3:26][C:27]1[C:32]([C:33]([N:17]2[CH2:18][CH2:19][CH:14]([CH:13]3[S:12][CH2:11][CH2:10][NH:9][C:8]4[N:4]([CH3:3])[N:5]=[C:6]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=5)[C:7]3=4)[CH2:15][CH2:16]2)=[O:34])=[CH:31][CH:30]=[CH:29][N:28]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 6433732-Methylnicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 136348417HCID 136348417, compound

Product 1

HCID 136348421HCID 136348421, compoundYield 71.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-methyl-4-(4-piperidyl)-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine dihydrochloride (0.10 g, 0.25 mmol, Preparation #4), 2-methylpyridine-3-carboxylic acid (0.0341 g, 0.25 mmol), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.072 g, 0.37 mmol), 1-hydroxybenzotriazole hydrate (0.0505 g, 0.37 mmol) and N,N-diisopropylethylamine (0.22 mL, 1.25 mmol) in DCM (50 mL) was stirred overnight at rt. Then the mixture was concentrated in vacuo and purified by column chromatography (SiO2, DCM/methanol/ammonium hydroxide 92:7.5:0.5) to give (2-methyl-3-pyridyl)-[4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]-1-piperidyl]methanone (0.080 g, 71%) as an off white solid: LC-MS (Table 1, Method a) Rt=1.50 min; m/z 449 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) 1.17-1.39 (2H, m) 1.44-1.64 (1H, m) 2.08-3.14 (10H, m) 3.22-3.55 (3H, m) 3.74-3.77 (3H, s) 4.58-4.78 (1H, br.d, J=13.0 Hz) 5.06-5.16 (1H, m) 7.05-7.20 (2H, m) 7.36-7.55 (1H, m) 7.62-7.72 (1H, m) 7.89 (1H br.t, J=9.0 Hz) 8.43-8.59 (2H, m).

Workup

  1. concentrationThen the mixture was concentrated in vacuo
  2. custompurified by column chromatography (SiO2, DCM/methanol/ammonium hydroxide 92:7.5:0.5)

Sources & evidence

ORD record
ord-fe4571fcdf3e4274837e0bc00e725371
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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