Triethylamine → HCID 136402449, compound

HRID 548385Notes

Reaction equation

HRID 548385 reaction equation
[Na+].[O:2]=[S:3]1(=[O:17])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][N:11]=2)[NH:6][C:5]([CH2:13][C:14]([O-])=[O:15])=[N:4]1.C([O:20][C:21]([C@H:23]1[C@@H:28]([NH:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[C@H:27]2[CH2:38][C@@H:24]1[CH2:25][CH2:26]2)=O)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[O:2]=[S:3]1(=[O:17])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][N:11]=2)[NH:6][C:5]([C:13]2[C:14](=[O:15])[N:29]([CH2:30][C:31]3[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=3)[C@@H:28]3[C@H:23]([C:21]=2[OH:20])[C@@H:24]2[CH2:38][C@H:27]3[CH2:26][CH2:25]2)=[N:4]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66658077(1S,2R,3S,4R)-3-(4-fluorobenzylamino)-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl esterHCID 66674440HCID 66674440, compound

Product 1

HCID 136402449HCID 136402449, compoundYield 6.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

The crude (1,1-dioxo-1,4-dihydro-1λ6-thia-2,4,8-triaza-naphthalen-3-yl)-acetic acid sodium salt (˜0.928 mmol), (1S,2R,3S,4R)-3-(4-fluoro-benzylamino)-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester (0.27 g, 0.928 mmol) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.494 g, 1.3 mmol) were combined and dissolved in anhydrous N,N-dimethylformamide (2 mL). The mixture was stirred at 25° C. for 1.5 h. Triethylamine (0.697 mL, 5 mmol) was added and the mixture was stirred at 50° C. for 16 h. Upon cooling, the mixture was diluted with ethyl acetate (100 mL), washed with saturated aqueous ammonium chloride solution (2×25 mL) and saturated aqueous brine solution (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting solid was triturated with ethyl acetate (˜15 mL) and the product solidified. The solid was collected by vacuum filtration and dried in vacuo for 16 h to afford the desired product, (1R,2S,7R,8S)-5-(1,1-dioxo-1,4-dihydro-1λ6-thia-2,4,8-triaza-naphthalen-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (0.03 g, 0.064 mmol, 6.9%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 0.92-1.05 (2H, m), 1.18-1.46 (4H, m), 2.26 (1H, d, J=3.1 Hz), 2.36 (1H, d, J=9.5 Hz), 2.45 (1H, d, J=3.0 Hz), 3.15 (1H, d, J=9.4 Hz), 4.13 (1H, d, J=15.6 Hz), 4.86 (1H, d, J=15.6 Hz), 7.01-7.05 (2H, m), 7.16-7.20 (2H, m), 7.39-7.42 (1H, m), 7.50 (1H, dd, J1=8.6 Hz, J2=1.6 Hz), 8.26 (1H, dd, J1=4.6 Hz, J2=1.5 Hz). LC-MS (ESI) calcd for C23H21FN4O4S 468.13, found 469.2 [M+H+].

Workup

  1. stirringthe mixture was stirred at 50° C. for 16 h
  2. temperatureUpon cooling
  3. washwashed with saturated aqueous ammonium chloride solution (2×25 mL) and saturated aqueous brine solution (25 mL)
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting solid was triturated with ethyl acetate (˜15 mL)
  8. filtrationThe solid was collected by vacuum filtration
  9. customdried in vacuo for 16 h

Sources & evidence

ORD record
ord-c351b9ed061045c58aaa4504deb37f7d
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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