Methanol → HCID 25153097, compound

HRID 1256665Notes

Reaction equation

HRID 1256665 reaction equation
C(OC(=O)[NH:10][C:11]1[C:12]([NH:23][C:24](=[O:35])[C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:34])[CH3:33])=[CH:27][CH:26]=2)=[N:13][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:15][CH:16]=1)C1C=CC=CC=1.CO.[H][H]>[Pd].CCOC(C)=O>[C:32]([NH:31][C:28]1[CH:29]=[CH:30][C:25]([C:24]([NH:23][C:12]2[C:11]([NH2:10])=[CH:16][CH:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:13]=2)=[O:35])=[CH:26][CH:27]=1)(=[O:34])[CH3:33]

Participants

6

Reactant 3

HCID 887MethanolHCID 59627863HCID 59627863, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 25153097HCID 25153097, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of benzyl(2-{[4-(acetylamino)benzoyl]amino}-6-phenylpyridin-3-yl)carbamate from the previous step (30 mg theoretical, 0.0626 mmol) and MeOH (100 uL) were treated with 10% palladium on carbon (cat) and the reaction was fitted with a hydrogen balloon. After one hour the reaction was diluted with EtOAc, filtered through celite and concentrated to a residue purified via reversed phase HPLC (30-70% MeCN in water with 0.05% TFA) to afford fractions concentrated via sublimation to afford the title compound as a light yellow solid and a TFA salt. 1H NMR (MeOH-d4, 600 MHz) δ 8.04 (d, J=8.8 Hz, 2H), 7.87 (d, J=7.3 Hz, 2H), 7.76 (t, 8.2 Hz, 3H), 7.62 (d, J=8.5 Hz, 1H), 7.51 (t, J=7.6 Hz, 2H), 7.45 (d, J=7.3 Hz, 1H), 2.18 (s, 3H); MS cal'd (M+H)+, exp 347 (M+H)+. The in vitro HDAC1 IC50 of this compound is 86 nM. The IC50 of this compound in HCT-116 cells is 2050 nM.

Workup

  1. filtrationfiltered through celite
  2. concentrationconcentrated to a residue
  3. custompurified via reversed phase HPLC (30-70% MeCN in water with 0.05% TFA)
  4. customto afford fractions
  5. concentrationconcentrated via sublimation

Sources & evidence

ORD record
ord-0f568179e4174ee9bb8aeb973045ff3f
Source dataset
uspto-grants-2013_06
Patent number
US08461189B2

Reaction notes

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