Triethylamine → HCID 71616986, compound

HRID 930882Notes

Reaction equation

HRID 930882 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][C:20]2[C:25]([F:26])=[CH:24][C:23]([F:27])=[CH:22][C:21]=2[F:28])=[C:6]([C:8]2[C:9]3[CH:18]=[CH:17][NH:16][C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.C(N(CC)CC)C.[CH3:36][NH:37][S:38](Cl)(=[O:40])=[O:39].[OH-].[Na+].[Cl-].[NH4+]>ClCCl.O1CCOCC1>[CH3:36][NH:37][S:38](=[O:40])(=[O:39])[NH:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][C:20]2[C:25]([F:26])=[CH:24][C:23]([F:27])=[CH:22][C:21]=2[F:28])=[C:6]([C:8]2[C:9]3[CH:18]=[CH:17][NH:16][C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 11789235N-Methylsulfamoyl chlorideHCID 86721046HCID 86721046, compound

Product 1

HCID 71616986HCID 71616986, compoundYield 11.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of Example 94b (76.3 mg, 0.198 mmol) and triethylamine (60.1 mg, 0.594 mmol) in dichloromethane (4 mL) was added dropwise methylsulfamoyl chloride (103 mg, 0.792 mmol), and the reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was mixed with dioxane (5 mL) and 1M aqueous sodium hydroxide (3 mL, 0.2 mmol) and heated at 70° C. for 1 hour. The reaction mixture cooled to ambient temperate and then neutralized with saturated aqueous ammonium chloride (50 mL) and the aqueous extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with saturated aqueous sodium chloride, dried (anhydrous magnesium sulfate), filtered, and concentrated. The residue was purified by preparative HPLC (C18, 10-80% acetonitrile in 0.1% TFA/water) to provide the title compound (11 mg, 11% yield). 1H NMR (300 MHz, DMSO-d6) ppm 12.04 (bs, 1H), 9.58 (s, 1H), 7.43-7.32 (m, 6H), 7.32-7.16 (m, 1H), 7.10 (dd, J=8.8, 2.7 Hz, 1H), 6.75 (d, J=8.8 Hz, 1H), 6.23 (t, J=2.3 Hz, 1H), 3.57 (bs, 3H), 2.35 (d, J=4.9 Hz, 3H). MS (ESI+) m/z 479.1 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. temperatureheated at 70° C. for 1 hour
  3. temperatureThe reaction mixture cooled
  4. extractionthe aqueous extracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride
  6. dry with materialdried (anhydrous magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC (C18, 10-80% acetonitrile in 0.1% TFA/water)

Sources & evidence

ORD record
ord-74c1374d0f024895ad9244611ca66a09
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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