Triethylamine → HCID 91160531, compound

HRID 1093145Notes

Reaction equation

HRID 1093145 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]1[C@@:19]2([CH3:23])[C:20]([CH3:22])([CH3:21])[C@H:16]([CH2:17][CH2:18]2)[CH2:15][N:14]2[C:24](=[O:34])[C:25]([OH:33])=[C:26]([C:28](OCC)=[O:29])[N:27]=[C:13]12)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42][NH2:43])=[CH:38][CH:37]=1.CCN(CC)CC>CCO.CCOCC>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C@@H:12]1[C@@:19]2([CH3:23])[C:20]([CH3:22])([CH3:21])[C@H:16]([CH2:17][CH2:18]2)[CH2:15][N:14]2[C:24](=[O:34])[C:25]([OH:33])=[C:26]([C:28](=[O:29])[NH:43][CH2:42][C:39]3[CH:40]=[CH:41][C:36]([F:35])=[CH:37][CH:38]=3)[N:27]=[C:13]12)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 57904778HCID 57904778, compound

Product 1

HCID 91160531HCID 91160531, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of ethyl (7S,10R)-11-(((benzyloxy)carbonyl)amino)-3-hydroxy-10,12,12-trimethyl-4-oxo-6,7,8,9,10,11-hexahydro-4H-7,10-methanopyrimido[1,2-a]azocine-2-carboxylate (1.4595 g, 3.11 mmol), (4-fluorophenyl)methanamine (1.143 mL, 10.00 mmol) and Et3N (1.394 mL, 10 mmol) in EtOH (25 mL) was heated at reflux for 14 h. the reaction mixture was then cooled, diluted with Et2O (100 mL), washed with 1N aq. HCl (1×25 mL), water (2×25 mL) followed by brine (25 mL), then dried (Na2SO4), filtered and concentrated to give a brown paste. The product was purified by preparative HPLC using a C18-column and 40-90% methanol/water (0.1 trifluoroacetic acid) to afford the title compound (0.367 g, 0.669 mmol, 22% yield) as a light brown solid. 1H NMR (500 MHz, CDCl3) δ: 12.21 (0.3 H, brs), 12.08 (0.7 H, s), 8.24 (0.3 H, brs), 7.71 (0.7 H, t, J=6.1 Hz), 7.18-7.38 (8 H, m), 6.92-7.05 (2 H, m), 4.98-5.21 (4 H, m), 4.52-4.58 (1H, m), 4.41-4.47 (1 H, m), 3.67 (0.7 H, d, J=15.6 Hz), 3.56 (0.3 H, d, J=15.6 Hz), 2.08 (0.7 H, t, J=8.1 Hz), 2.01-2.06 (0.3 H, m), 1.73-1.87 (2 H, m), 1.40-1.49 (1H, m), 1.37 (2 H, s), 1.28-1.35 (1 H, m), 1.25 (1 H, s), 1.00 (2 H, s), 0.99 (2 H, s), 0.95 (1 H, s), 0.92 (1 H, s). LCMS (M+H) calcd for C30H34FN4O5: 549.25; found: 549.28. Purity: >96%.

Workup

  1. temperatureat reflux for 14 h. the reaction mixture
  2. temperaturewas then cooled
  3. washwashed with 1N aq. HCl (1×25 mL), water (2×25 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a brown paste
  8. customThe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-ef3369e74ead48feaae992ee3c183a2c
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

Loading…