Ethanol → 4-{2-[3-amino-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-chlorophenoxy}-5-chloro-2-fluoro-N-(methoxymethyl)-N-pyrimidin-4-ylbenzenesulfonamide

HRID 1692365Notes

Reaction equation

HRID 1692365 reaction equation
[Cl:1][C:2]1[C:3]([O:22][C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[C:30]2[C:31]([N+:41]([O-])=O)=[N:32][N:33]([CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][O:36]3)[CH:34]=2)=[CH:4][C:5]([F:21])=[C:6]([S:8]([N:11]([CH2:18][O:19][CH3:20])[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)(=[O:10])=[O:9])[CH:7]=1.C(O)C.[Cl-].[NH4+]>[Fe]>[NH2:41][C:31]1[C:30]([C:24]2[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=2[O:22][C:3]2[C:2]([Cl:1])=[CH:7][C:6]([S:8]([N:11]([CH2:18][O:19][CH3:20])[C:12]3[CH:17]=[CH:16][N:15]=[CH:14][N:13]=3)(=[O:10])=[O:9])=[C:5]([F:21])[CH:4]=2)=[CH:34][N:33]([CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[N:32]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 594365105-chloro-4-(4-chloro-2-(3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenoxy)-2-fluoro-N-(methoxymethyl)-N-(pyrimidin-4-yl)benzenesulfonamide

Product 1

HCID 594365744-{2-[3-amino-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-chlorophenoxy}-5-chloro-2-fluoro-N-(methoxymethyl)-N-pyrimidin-4-ylbenzenesulfonamideYield 97.8%

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Conditions

Temperature
80 °C

Procedure

To a solution of 5-chloro-4-(4-chloro-2-(3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenoxy)-2-fluoro-N-(methoxymethyl)-N-(pyrimidin-4-yl)benzenesulfonamide (80 mg, 0.1 mmol) in ethanol (4 mL, 70 mmol) was added saturated aqueous ammonium chloride solution (0.4 mL, 6 mmol) and iron (328 mg, 5.87 mmol). The reaction solution was heated at 80° C. for 20 minutes then filtered. Saturated aqueous sodium bicarbonate was added until the pH was 9. The mixture was concentrated in vacuo to remove the ethanol. Water was added and the mixture was extracted three times with dichloromethane. The combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified on silica gel (hexane to 100% ethyl acetate gradient) to give 61 mg of a colorless oil.

Workup

  1. filtrationthen filtered
  2. additionSaturated aqueous sodium bicarbonate was added until the pH was 9
  3. concentrationThe mixture was concentrated in vacuo
  4. customto remove the ethanol
  5. additionWater was added
  6. extractionthe mixture was extracted three times with dichloromethane
  7. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified on silica gel (hexane to 100% ethyl acetate gradient)

Sources & evidence

ORD record
ord-db205a2170f34c81aba4eb0ecc96d95a
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

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