Acetic Acid → HCID 124019247, compound

HRID 1056989Notes

Reaction equation

HRID 1056989 reaction equation
[Br:1][C:2]1[C:3]([NH:39][CH3:40])=[C:4]([N+:36]([O-])=O)[C:5]([O:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])=[C:6]([C:8]2[C:9]3[CH:18]=[N:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.C(O)(=O)C>O1CCCC1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C.[Fe]>[NH2:36][C:4]1[C:5]([O:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])=[C:6]([C:8]2[C:9]3[CH:18]=[N:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:24])([CH3:25])[CH3:26])[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=[C:2]([Br:1])[C:3]=1[NH:39][CH3:40]

Participants

7

Reactant 2

HCID 176Acetic AcidHCID 123226035HCID 123226035, compound

Product 1

HCID 124019247HCID 124019247, compoundYield 52.3%

Reagents, catalysts & solvents 4

HCID 23925IronCatalyst2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 4-[5-bromo-2-(2,4-difluorophenoxy)-4-(methylamino)-3-nitrophenyl]-6-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.209 g, 0.328 mmol) in tetrahydrofuran (1.38 mL) was treated with iron (0.183 g, 3.28 mmol), followed by the addition of acetic acid (1.38 mL, 24.3 mmol). The resultant reaction mixture was warmed to 60° C. and stirred at 60° C. for 1.5 h. The reaction mixture was treated with iron (0.0917 g, 1.64 mmol) and stirred at 60° C. for 14 h, after which time the reaction mixture was filtered through the pad of Celite and washed with ethyl acetate. The filtrate was concentrated in vacuo to give a crude residue. The crude residue was diluted with saturated solution of sodium bicarbonate and ethyl acetate. Layers were separated and the organic layer was washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo to give a crude residue. Purification by flash column chromatography (100% hexanes to 40% EtOAc/hexanes) gave the desired product (104 mg, 52%) as a white solid. LCMS calculated for C26H31BrF2N5O3Si (M+H)+: m/z=606.1, 608.1. found: 606.0, 608.0.

Workup

  1. customThe resultant reaction mixture
  2. stirringstirred at 60° C. for 14 h
  3. filtrationafter which time the reaction mixture was filtered through the pad of Celite
  4. washwashed with ethyl acetate
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto give a crude residue
  7. customLayers were separated
  8. washthe organic layer was washed with brine
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give a crude residue
  13. customPurification by flash column chromatography (100% hexanes to 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c1466ac9407f4fa48cdbfd7626f70d78
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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