4-Methylmorpholine → HCID 57436516, compound

HRID 502582Notes

Reaction equation

HRID 502582 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=[C:38]([S:42]([NH:45][C:46]([CH3:49])([CH3:48])[CH3:47])(=[O:44])=[O:43])[CH:39]=[CH:40][CH:41]=[C:36]2[S:35][N:34]=1>C(Cl)Cl>[C:46]([NH:45][S:42]([C:38]1[C:37]2[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)=[N:34][S:35][C:36]=2[CH:41]=[CH:40][CH:39]=1)(=[O:44])=[O:43])([CH3:49])([CH3:48])[CH3:47]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 120854-Iodobenzoic acidHCID 76257Diethyl cyanophosphonateHCID 57436513HCID 57436513, compound

Product 1

HCID 57436516HCID 57436516, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 4-iodobenzoic acid (210 mg, 0.8 mmol) in methylene chloride (2 mL), diethyl cyanophosphonate (120 μL, 0.8 mmol) and 4-methylmorpholine (172 μL, 1.6 mmol) were added at room temperature and allowed to stir for 15 min. A solution of 3-(3-aminopropylamino)-N-tert-butylbenzo[d]isothiazole-4-sulfonamide (243 mg, 0.7 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 over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with 1:1 ethyl acetate:hexanes, followed by 7:3 ethyl acetate:hexanes provided N-(3-(4-(N-tert-butylsulfamoyl)benzo[d]isothiazol-3-ylamino)propyl)-4-iodobenzamide (365 mg) as a yellow foam. 1H NMR (300 MHz, CDCl3): 8.01 (dd, 1H), 7.96 (dd, 1H), 7.80 (d, 2H), 7.59 (d, 2H), 7.43-7.49 (m, 2H), 6.10 (t, 1H), 4.98 (s, 1H), 3.71 (dd, 2H), 3.59 (dd, 2H), 1.92-2.00 (m, 2H), 1.25 ppm (s, 9H). MW=572 confirmed by LC-MS, tr=13.85 min (Method Y) MH+=573.

Workup

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

Sources & evidence

ORD record
ord-bdb281f55fd6405ea9b02c03a3f54427
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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