Methanol → 4-[3,4-Diamino-2-(2,4-difluorophenoxy)phenyl]-6-methyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

HRID 1056936Notes

Reaction equation

HRID 1056936 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:18]=[CH:17][N:16]([S:19]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)(=[O:21])=[O:20])[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)=[C:4]([O:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])[C:3]=1[N+:38]([O-])=O.CO.[Cl-].[NH4+]>C(OCC)(=O)C.[Zn]>[NH2:38][C:3]1[C:4]([O:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])=[C:5]([C:8]2[C:9]3[CH:18]=[CH:17][N:16]([S:19]([C:22]4[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][CH:27]=4)(=[O:20])=[O:21])[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:6]=[CH:7][C:2]=1[NH2:1]

Participants

6

Reactant 3

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 1180937554-[4-amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

Product 1

HCID 1180938284-[3,4-Diamino-2-(2,4-difluorophenoxy)phenyl]-6-methyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-oneYield 97.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 4-[4-amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (108 mg, 0.191 mmol) in ethyl acetate (0.46 mL) was treated with methanol (0.46 mL) and saturated aqueous ammonium chloride solution (0.166 mL, 2.48 mmol) and cooled to 0° C. The reaction mixture was treated with zinc (99.7 mg, 1.52 mmol) and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, filtered through a pad of Celite, and the solids were washed with ethyl acetate. The filtrate was washed with saturated sodium bicarbonate solution (40 mL). The aqueous layer was separated and re-extracted with ethyl acetate (40 mL). The combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated to give a crude residue. Purification by flash column chromatography (40% EtOAc/hexanes to 100% EtOAc) gave the desired product (100 mg, 93%) as a brown oil. LCMS calculated for C27H23F2N4O4S (M+H)+: m/z=537.1. found: 537.1.

Workup

  1. filtrationfiltered through a pad of Celite
  2. washthe solids were washed with ethyl acetate
  3. washThe filtrate was washed with saturated sodium bicarbonate solution (40 mL)
  4. customThe aqueous layer was separated
  5. extractionre-extracted with ethyl acetate (40 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a crude residue
  11. customPurification by flash column chromatography (40% EtOAc/hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-9046ae82f30e42c284f10c2b17b6d489
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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