Methanol → HCID 58020111, compound

HRID 1632078Notes

Reaction equation

HRID 1632078 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH:15]([F:17])[F:16])=[CH:12][CH:11]=[C:10]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([C:25]#[N:26])=[N:23][CH:24]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.CO>[Pd]>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH:15]([F:16])[F:17])=[CH:12][CH:11]=[C:10]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([CH2:25][NH2:26])=[N:23][CH:24]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 57703713HCID 57703713, compound

Product 1

HCID 58020111HCID 58020111, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

In a 40 mL vial equipped with a stir bar was placed 5-(3′-Chloro-6-difluoromethoxy-biphenyl-3-ylmethyl)-pyridine-2-carbonitrile (I-148, 860 mg, 2.32 mmol), methanol (20 mL) concentrated HCl (967 uL, 11.6 mmol) and 10% Pd/C. The reaction is allowed to stir at ambient temperature for 6 hours under a hydrogen atmosphere. After filtering the mixture through Celite, the filtrate is concentrated, diluted with 0.5M HCl (20 mL) and water (20 mL) followed by extractions with ethyl acetate (2×50 mL). The organic portions were combined, dried (MgSO4), concentrated and purified by silica gel column chromatography utilizing 10% 1M NH3 in MeOH/dichloromethane as the eluent to produce 121 mg of P-596 as a pale yellow solid in 14% yield.

Workup

  1. customIn a 40 mL vial equipped with a stir bar
  2. filtrationAfter filtering the mixture through Celite
  3. concentrationthe filtrate is concentrated
  4. additiondiluted with 0.5M HCl (20 mL) and water (20 mL)
  5. extractionfollowed by extractions with ethyl acetate (2×50 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. custompurified by silica gel column chromatography utilizing 10% 1M NH3 in MeOH/dichloromethane as the eluent
  9. customto produce 121 mg of P-596 as a pale yellow solid in 14% yield

Sources & evidence

ORD record
ord-39c4976fa41d4ed0825059a080e0dd14
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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