Triethylamine → [4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl]-acetic acid ethyl ester

HRID 1056854Notes

Reaction equation

HRID 1056854 reaction equation
Cl.[CH:2]1([NH:5][CH3:6])[CH2:4][CH2:3]1.CCN(CC)CC.[CH2:14]([O:16][C:17](=[O:34])[CH2:18][C:19]1[N:32]=[C:31](Cl)[C:22]2[C:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]=3[S:30][C:21]=2[N:20]=1)[CH3:15]>CO>[CH2:14]([O:16][C:17](=[O:34])[CH2:18][C:19]1[N:32]=[C:31]([N:5]([CH:2]2[CH2:4][CH2:3]2)[CH3:6])[C:22]2[C:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]=3[S:30][C:21]=2[N:20]=1)[CH3:15]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 18546974N-methylcyclopropanamine hydrochlorideHCID 89719628(4-chloro-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl)-acetic acid ethyl ester

Product 1

HCID 89719440[4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl]-acetic acid ethyl esterYield 81.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Cyclopropyl-methyl amine HCl (1.32 g, 0.0123 mol) and Et3N (2.4 g, 0.0246 mol) were added to a solution of (4-chloro-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl)-acetic acid ethyl ester (2 g, 0.00615 mol) in 20 ml of methanol and the mixture was stirred for 18 h at ambient temperature. The methanol was removed under vacuum and the crude was purified by chromatography on silica gel using 10% ethyl acetate in hexanes to give [4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl]-acetic acid ethyl ester (1.8 g, 81%) as a pale yellow liquid. 1H NMR (400 MHz, CDCl3): δ 4.18 (q, 2H), 3.89 (s, 2H), 2.92-3.00 (m, 5H), 2.78-2.90 (m, 3H), 1.85-1.92 (m, 2H), 1.68-1.77 (m, 2H), 1.60-1.67 (m, 2H), 1.25 (t, 3H), 0.68-0.75 (m, 2H), 0.40-0.47 (m, 2H); LC-MS: [M+H]: =359.9 m/z.

Workup

  1. customThe methanol was removed under vacuum
  2. customthe crude was purified by chromatography on silica gel using 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-886b4157a54842988a055f92a2f0067e
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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