Cesium carbonate → HCID 11856677, compound

HRID 736822Notes

Reaction equation

HRID 736822 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[C:17](=[O:18])[C@:16]3([CH3:19])[C@H:12]2[CH2:13][CH2:14][CH2:15]3)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:31]=[C:30]([CH3:38])[CH:29]=1.F[P-](F)(F)(F)(F)F.[N:46]1([O:55][P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.NO>C(#N)C.C(OCC)(=O)C.CN(C=O)C.C(N(CC)CC)C.O>[OH:55][NH:46][C:17]([C@@:16]1([CH3:19])[CH2:15][CH2:14][CH2:13][C@H:12]1[NH:11][S:8]([C:5]1[CH:6]=[CH:7][C:2]([O:1][CH2:27][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]=[C:30]([CH3:38])[CH:29]=2)=[CH:3][CH:4]=1)(=[O:10])=[O:9])=[O:18]

Participants

11

Reactant 5

HCID 10796Cesium carbonateHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 443297Hydroxyamine hydrochlorideHCID 115357194-(Chloromethyl)-2-methylquinolineHCID 68817298HCID 68817298, compound

Product 1

HCID 11856677HCID 11856677, compoundYield 24%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

To (1S,5R)-6-[(4-hydroxyphenyl)sulfonyl]-1-methyl-6-azabicyclo[3.2.0]heptan-7-one (291 mg, 1.04 mmol) was added cesium carbonate (1.011 g, 2.70 mmol) and 4-(chloromethyl) -2-methylquinoline (498 mg, 2.18 mmol) in acetonitrile (2 mL), with DMF to aid solubility. This reaction was stirred at room temperature overnight with partial β-lactam hydrolysis being observed. Water was then added to the reaction mixture and it was heated in a microwave for 5 min at 150° C. The mixture was then diluted with ethyl acetate, washed with water and brine. The aqueous layers were acidified to pH 4 with 1 M HCl and then extracted with ethyl acetate. The combined organic extracts were dried over Na2SO4)] and concentrated to give an orange oil that was carried on without further purification. The orange oil was combined with BOP (500 mg, 1.13 mmol), hydroxylamine hydrochloride (179 mg, 2.56 mmol), and triethylamine (710 μL) in DMF (3 mL). This mixture was stirred at room temperature overnight, the solids were filtered and the filtrate was purified by HPLC eluting with a gradient of 15-100% MeCN/H2O (10 min) to give (1S,2R)-N-hydroxy-1-methyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxamide (107 mg, 0.228 mmol, 24%) as a colorless solid. LCMS (M−H): 1.72 min; 468.4; 1H NMR (400 MHz, DMSO-D6) δ ppm 1.07 (s, 3H) 1.41 (m, 3H) 1.54 (s, 1H) 1.99 (d, J=1.01 Hz, 1H) 2.60-2.70 (m, 3H) 3.13 (s, 1H) 5.72 (s, 2H) 7.27-7.36 (m, 2H) 7.53-7.65 (m, 2H) 7.73-7.85 (m, 2H) 7.98 (d, J=8.34 Hz, 1H) 8.10 (s, 1H).

Workup

  1. washwashed with water and brine
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried over Na2SO4)] and
  4. concentrationconcentrated
  5. customto give an orange oil that
  6. customwas carried on without further purification
  7. filtrationthe solids were filtered
  8. customthe filtrate was purified by HPLC
  9. washeluting with a gradient of 15-100% MeCN/H2O (10 min)

Sources & evidence

ORD record
ord-4626741b22cd4e418af37ea808abc53e
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

Loading…