Triethylamine → HCID 136334013, compound

HRID 2409498Notes

Reaction equation

HRID 2409498 reaction equation
Cl.Cl.Cl[C:4]1[CH:9]=[CH:8][NH:7][C:6](=[O:10])[C:5]=1[C:11]1[NH:12][C:13]2[C:21]([N:22]=1)=[CH:20][C:19]1[C:18](=[O:23])[N:17]([CH2:24][CH2:25][CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH2:16][C:15]=1[CH:14]=2.Cl.[CH3:33][C@H:34]([NH2:41])[CH2:35][C:36]1[S:37][CH:38]=[CH:39][CH:40]=1.CCN(CC)CC>CCO>[CH3:33][C@H:34]([NH:41][C:4]1[CH:9]=[CH:8][NH:7][C:6](=[O:10])[C:5]=1[C:11]1[NH:12][C:13]2[C:21]([N:22]=1)=[CH:20][C:19]1[C:18](=[O:23])[N:17]([CH2:24][CH2:25][CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH2:16][C:15]=1[CH:14]=2)[CH2:35][C:36]1[S:37][CH:38]=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 86677137HCID 86677137, compoundHCID 136334014HCID 136334014, compound

Product 1

HCID 136334013HCID 136334013, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(4-chloro-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(3-pyrrolidin-1-yl-propyl)-6,7-dihydro-1H-1,3,6-triaza-s-indacen-5-one dihydrochloride (17) (2.2 g, 4.9 mmol), (1S)-1-methyl-2-thien-2-ylethylamine hydrochloride (13b) (870 mg, 4.9 mmol) and Et3N (3.44 mL, 24.5 mmol) in EtOH (20 mL) was heated at 100° C. for 12 h. The mixture was concentrated, diluted with water (20 mL) and extracted with CHCl3 (5×20 mL) the combined organic layer was dried, concentrated to a residue that was purified on silica gel column using 10% NH4OH/methanol in CH2Cl2 to get pure 2-[4-((S)-1-methyl-2-thiophen-2-yl-ethylamino)-2-oxo-1,2-dihydro-pyridin-3-yl]-6-(3-pyrrolidin-1-yl-propyl)-6,7-dihydro-1H-1,3,6-triaza-s-indacen-5-one (18a) (1.2 g, 51%). 1H NMR (DMSO-d6) δ 1.33 (d, 3H, J=3.0 Hz), 1.55-1.85 (m, 6H), 2.3-2.45 9 m, 6H), 3.15-3.25− (m, 2H), 3.56 (t, 2H, J=6.0 Hz), 3.95-4.15 (m, 1H), 4.51 (s, 2H), 6.15 (d, 1H, J=9.0 Hz), 6.91-6.96 (m, 1H), 7.05 (t, 1H, J=3.0 Hz), 7.31-7.36 (m, 2H), 7.66 (s, 0.5H), 7.79 (d, 1H, J=3.0 Hz), 7.93 (s, 0.5H), 11.14 (d, 1H, J=9.0 Hz), 11.24 (bs, 1H). ESI-MS m/z 517.67 (M++1).

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with water (20 mL)
  3. extractionextracted with CHCl3 (5×20 mL) the combined organic layer
  4. customwas dried
  5. concentrationconcentrated to a residue that
  6. customwas purified on silica gel column

Sources & evidence

ORD record
ord-a1108fd617dd43b0ad92f7029f49696c
Source dataset
uspto-grants-2014_08
Patent number
US08815906B2

Reaction notes

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