4-Methylmorpholine → HCID 57436517, compound

HRID 502585Notes

Reaction equation

HRID 502585 reaction equation
[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.C(P(=O)(OCC)OCC)#N.CN1CCOCC1.[NH2:28][CH2:29][CH2:30][CH2:31][NH:32][C:33]1[C:37]2[CH:38]=[CH:39][CH:40]=[C:41]([S:42]([NH:45][C:46]([CH3:49])([CH3:48])[CH3:47])(=[O:44])=[O:43])[C:36]=2[S:35][N:34]=1>C(Cl)Cl>[C:46]([NH:45][S:42]([C:41]1[C:36]2[S:35][N:34]=[C:33]([NH:32][CH2:31][CH2:30][CH2:29][NH:28][C:6](=[O:8])[C:5]3[CH:4]=[CH:3][C:2]([I:1])=[CH:10][CH:9]=3)[C:37]=2[CH:38]=[CH:39][CH:40]=1)(=[O:43])=[O:44])([CH3:49])([CH3:48])[CH3:47]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 120854-Iodobenzoic acidHCID 76257Diethyl cyanophosphonateHCID 57436514HCID 57436514, compound

Product 1

HCID 57436517HCID 57436517, compoundYield 77.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 4-iodobenzoic acid (270 mg, 0.8 mmol) in methylene chloride (2 mL), diethyl cyanophosphonate (130 μL, 0.9 mmol) and 4-methylmorpholine (182 μL, 1.7 mmol) were added at room temperature and allowed to stir for 15 min. A solution of 3-(3-aminopropylamino)-N-t-butylbenzo[d]isothiazole-7-sulfonamide (270 mg, 0.8 mmol) in methylene chloride (4 mL) was then added and the resulting reaction mixture was allowed to stir overnight. The reaction mixture with diluted with methylene chloride (20 mL), washed with 10% HCl aqueous solution and brine, dried anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with 6:4 ethyl acetate:hexanes provided N-(3-(7-(N-tert-butylsulfamoyl)benzo[d]isothiazol-3-ylamino)propyl)-4-iodobenzamide (355 mg). 1H NMR (300 MHz, CDCl3): 8.01 (dd, 1H), 7.96 (d, 1H), 7.78 (d, 2H), 7.59 (d, 2H), 7.53 (t, 1H), 7.44 (t, 1H), 6.15 (t, 1H), 5.09 (s, 1H), 3.70 (dd, 2H), 3.57 (dd, 2H), 1.90-1.99 (m, 2H), 1.24 ppm (s, 9H). MS (m/z): 573 (M+H)+ confirmed by LC-MS, tr=13.92 min (Method Y) MW=572 confirmed by LC-MS, tr=13.92 min (Method Y) MH+=573.

Workup

  1. customthe resulting reaction mixture
  2. stirringto stir overnight
  3. washwashed with 10% HCl aqueous solution and brine, dried anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography
  7. washon silica gel, eluting with 6:4 ethyl acetate

Sources & evidence

ORD record
ord-fb0cd955cad0481ca652f50e1cc5d579
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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