Acetic Acid → HCID 90067508, compound

HRID 1057067Notes

Reaction equation

HRID 1057067 reaction equation
[CH2:1]([N:8]1[CH:13]=[C:12]([C:14]2[CH:19]=[C:18]([N:20]3[CH2:24][CH2:23][C:22]([F:26])([F:25])[CH2:21]3)[N:17]=[C:16]([NH:27][C:28]3[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][N:29]=3)[CH:15]=2)[CH2:11][CH2:10][CH2:9]1)C1C=CC=CC=1.CO.C(OCC)(=O)C.C(O)(=O)C>[OH-].[OH-].[Pd+2]>[F:26][C:22]1([F:25])[CH2:23][CH2:24][N:20]([C:18]2[N:17]=[C:16]([NH:27][C:28]3[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][N:29]=3)[CH:15]=[C:14]([CH:12]3[CH2:11][CH2:10][CH2:9][N:8]([CH3:1])[CH2:13]3)[CH:19]=2)[CH2:21]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 8857Ethyl AcetateHCID 90067635HCID 90067635, compound

Product 1

HCID 90067508HCID 90067508, compoundYield 4.4%

Reagents, catalysts & solvents 1

HCID 9942167Palladium hydroxideCatalyst

Procedure

A suspension of 4-(1-benzyl-3,4-dihydro-2H-pyridin-5-yl)-6-(3,3-difluoropyrrolidin-1-yl)-N-[4-(trifluoromethyl)-2-pyridyl]pyridin-2-amine (250 mg, 0.4850 mmol) and palladium hydroxide on activated charcoal (85 mg, 0.25 equiv., 0.1212 mmol) in methanol (20 ml, 500 mmol) and ethyl acetate (20 ml, 204 mmol) was charged with H2 balloon. The reaction was kept stirring for 48 h, while LCMS indicated olefin was reduced. The catalyst was filtered off, and new portion of catalyst was refilled, followed by addition of acetic acid (0.556 mL, 20 equiv., 9.699 mmol). The reaction was stirred with H2 balloon overnight. LCMS showed both m/z 442 and 456. The catalyst was filtered off, and the solvent was evaporated to dryness. The residue was submitted for HPLC purification to yield 4.7 mg (4.4%) off-white powder. LCMS: m/z 442 (M+H).

Workup

  1. additionwas charged with H2 balloon
  2. filtrationThe catalyst was filtered off
  3. additionnew portion of catalyst was refilled
  4. stirringThe reaction was stirred with H2 balloon overnight
  5. filtrationThe catalyst was filtered off
  6. customthe solvent was evaporated to dryness
  7. customThe residue was submitted for HPLC purification

Sources & evidence

ORD record
ord-489b27637d3641579e91a81af23453b7
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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