Triethylamine → N'-(2-((4-Fluoro-2-(5-methyl-1H-1,2,3-triazol-1-yl)benzyl)carbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

HRID 1093130Notes

Reaction equation

HRID 1093130 reaction equation
[CH3:1][N:2]([C:4](=[O:28])[C:5]([NH:7][C:8]12[CH2:16][CH2:15][CH:12]([CH2:13][CH2:14]1)[CH2:11][N:10]1[C:17](=[O:27])[C:18]([OH:26])=[C:19]([C:21]([O:23]CC)=O)[N:20]=[C:9]21)=[O:6])[CH3:3].Cl.Cl.[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][NH2:39])=[C:34]([N:40]2[C:44]([CH3:45])=[CH:43][N:42]=[N:41]2)[CH:33]=1.C(N(CC)CC)C>C(O)C>[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][NH:39][C:21]([C:19]2[N:20]=[C:9]3[C:8]4([NH:7][C:5](=[O:6])[C:4]([N:2]([CH3:3])[CH3:1])=[O:28])[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16]4)[CH2:11][N:10]3[C:17](=[O:27])[C:18]=2[OH:26])=[O:23])=[C:34]([N:40]2[C:44]([CH3:45])=[CH:43][N:42]=[N:41]2)[CH:33]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 57904884Ethyl 10-(((dimethylamino)(oxo)acetyl)amino)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylateHCID 131729489(4-fluoro-2-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl)methanamine, bis-hydrochloride salt

Product 1

HCID 57905230N'-(2-((4-Fluoro-2-(5-methyl-1H-1,2,3-triazol-1-yl)benzyl)carbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamideYield 23.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of ethyl 10-(((dimethylamino)(oxo)acetyl)amino)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylat (30 mg, 0.076 mmol), (4-fluoro-2-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl)methanamine, bis-hydrochloride salt (42.7 mg, 0.153 mmol) and triethylamine (0.1 ml, 0.717 mmol) in ethanol (2 mL) was heated at 90° C. for 18 h. The reaction mixture was then cooled, concentrated and purified on preparative reversed phase HPLC to afford the title compound (10 mg, 21% yield) as an off-white solid. 1H NMR (500 MHz, CDCl3) δ: 1.66-1.77 (m, 2 H) 1.90-2.01 (m, 2 H) 2.14-2.24 (m, 2 H) 2.27 (s, 3 H) 2.39-2.47 (m, 2 H) 2.50 (br. s., 1 H) 2.89 (s, 3 H) 3.19 (s, 3 H) 4.15 (d, J=3.97 Hz, 2 H) 4.23 (d, J=6.41 Hz, 2 H) 6.99 (dd, J=8.24, 2.44 Hz, 1 H) 7.26-7.33 (m, 2 H) 7.62-7.68 (m, 2 H) 8.86 (t, J=6.10 Hz, 1H) 11.73 (br. s., 1 H). LCMS (M+H)=553.22. HPLC purity: >95%.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. concentrationconcentrated
  3. custompurified on preparative reversed phase HPLC

Sources & evidence

ORD record
ord-2282e486dafc44f7b220bbd4fffec865
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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