Dimethylformamide → HCID 118380176, compound

HRID 708540Notes

Reaction equation

HRID 708540 reaction equation
[CH3:1][O:2][C:3]1[CH:46]=[C:45]([O:47][CH3:48])[CH:44]=[CH:43][C:4]=1[CH2:5][N:6]1[C:9](=[O:10])[C@@H:8]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:7]1[CH2:22][N:23]1[N:27]=[C:26]2[CH2:28][N:29](S(C3C=CC=CC=3[N+]([O-])=O)(=O)=O)[CH2:30][C:25]2=[N:24]1.[C:49](=[O:52])([O-])[O-:50].[K+].[K+].[C:55]1(S)[CH:60]=[CH:59]C=CC=1.[CH3:62]N(C=O)C>CCOC(C)=O>[CH2:14]([O:13][C:12]([NH:11][C@@H:8]1[C:9](=[O:10])[N:6]([CH2:5][C:4]2[CH:43]=[CH:44][C:45]([O:47][CH3:48])=[CH:46][C:3]=2[O:2][CH3:1])[C@@H:7]1[CH2:22][N:23]1[N:24]=[C:25]2[CH2:30][N:29]([C:49]([O:50][C:60]([CH3:59])([CH3:55])[CH3:62])=[O:52])[CH2:28][C:26]2=[N:27]1)=[O:21])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 131733851HCID 131733851, compound

Product 1

HCID 118380176HCID 118380176, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a slurry of benzyl ((2R,3S)-1-(2,4-dimethoxybenzyl)-2-((5-((2-nitrophenyl)sulfonyl)-5,6-dihydropyrrolo[3,4-d][1,2,3]triazol-2(4H)-yl)methyl)-4-oxoazetidin-3-yl)carbamate (241 mg, −50%/wt, −0.178 mmol) and potassium carbonate (77.4 mg, 0.560 mmol) in DMF (3.0 mL) was added thiophenol (23.8 μl, 0.231 mmol). After stirring at rt for 2 h, Boc-anhydride (78 mg, 0.36 mmol) was added. After an additional 2 h, the slurry was diluted with EtOAc and washed with saturated NaHCO3 (aq). The aqueous layer was extracted with EtOAc (2×) and the combined organic layers were washed with LiCl (5% aq), brine, dried over Na2SO4 and concd in vacuo. The crude residue was combined with the residues from 2 like transformations (15 mg and 20 mg scales) and purified via silica gel chromatography (EtOAc-Heptane, 0-100%) to afford the title compound (85.5 mg, 81% combined). Rt=0.96 min, m/z=593.2 (M+1) Method 2m_acidic. 1H NMR (500 MHz, DMSO-d6) δ 8.21 (d, J=9.6 Hz, 1H), 7.40-7.27 (m, 5H), 6.92 (d, J=8.3 Hz, 1H), 6.49 (d, J=2.1 Hz, 1H), 6.40 (d, J=8.3 Hz, 1H), 5.04 (s, 2H), 5.00 (dd, J=9.6, 5.1 Hz, 1H), 4.65 (dd, J=14.0, 7.1 Hz, 1H), 4.56 (dd, J=4.1, 6.2 Hz, 1H), 4.38-4.24 (m, 5H), 4.12 (q, J=6.2 Hz, 1H), 3.86 (d, J=15.1 Hz, 1H), 3.74 (s, 3H), 3.72 (s, 3H), 1.46 (s, 9H).

Workup

  1. waitAfter an additional 2 h
  2. washwashed with saturated NaHCO3 (aq)
  3. extractionThe aqueous layer was extracted with EtOAc (2×)
  4. washthe combined organic layers were washed with LiCl (5% aq), brine
  5. dry with materialdried over Na2SO4 and concd in vacuo
  6. custompurified via silica gel chromatography (EtOAc-Heptane, 0-100%)

Sources & evidence

ORD record
ord-1f99a1cd8a234df9a1b97ffa17d873e5
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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