Dimethylamine → 2-[4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl]-N,N-dimethyl-acetamide

HRID 1056856Notes

Reaction equation

HRID 1056856 reaction equation
C[CH2:2][N:3]=[C:4]=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CNC.[CH:25]1([N:28]([CH3:47])[C:29]2[C:34]3[C:35]4[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][C:41]=4[S:42][C:33]=3[N:32]=[C:31]([CH2:43][C:44]([OH:46])=O)[N:30]=2)[CH2:27][CH2:26]1>C1COCC1>[CH:25]1([N:28]([CH3:47])[C:29]2[C:34]3[C:35]4[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][C:41]=4[S:42][C:33]=3[N:32]=[C:31]([CH2:43][C:44]([N:3]([CH3:4])[CH3:2])=[O:46])[N:30]=2)[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 71667913[4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diazabenz[a]azulen-2-yl]-acetic acid

Product 1

HCID 716679142-[4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl]-N,N-dimethyl-acetamideYield 58.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The EDCI (0.477 g, 0.00241 mol), HOBt (0.22 g, 0.00144 mol) and N,N-dimethyl amine in THF (2 M, 1.2 ml, 0.00241 mol) were added to a solution of [4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diazabenz[a]azulen-2-yl]-acetic acid (0.4 g, 0.0012 mol) in 10 ml of THF. The mixture was stirred for 3 h at room temperature then concentrated under vacuum. The crude was purified by chromatography on silica gel using 2% MeOH-DCM to give 2-[4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl]-N,N-dimethyl-acetamide (0.25 g, 58%) as pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 3.98 (s, 2H), 3.06 (s, 3H), 2.92-3.02 (m, 8H), 2.84-2.88 (m, 2H), 2.72-2.83 (m, 1H), 1.82-1.90 (m, 2H), 1.67-1.78 (m, 2H), 1.50-1.60 (m, 2H), 0.62-0.72 (m, 2H), 0.40-0.48 (m, 2H); LC-MS: [M+H]=359.4 m/z.

Workup

  1. concentrationthen concentrated under vacuum
  2. customThe crude was purified by chromatography on silica gel using 2% MeOH-DCM

Sources & evidence

ORD record
ord-0278527592744e34b60acccffd4a4dad
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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