Formic Acid → HCID 68520408, compound

HRID 639915Notes

Reaction equation

HRID 639915 reaction equation
C([N:4]1[C:13]([C:14]#[N:15])=[C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:23][CH:24]([F:26])[F:25])[CH:10]=2)[C:5]1=[O:27])C=C.C(N(CC)CC)C.C(O)=O>O1CCOCC1>[F:26][CH:24]([F:25])[O:23][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[C:5](=[O:27])[NH:4][C:13]([C:14]#[N:15])=[C:12]2[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=1

Participants

5

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 68518094HCID 68518094, compound

Product 1

HCID 68520408HCID 68520408, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-allyl-6-(difluoromethoxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile in 10 mL dioxane were added triethylamine (0.363 mL) and formic acid (0.079 mL). The solution was sparged with argon for 10 min, then Pd(PPh3)4 was added, and the reaction was heated to 100 C for 2 h. The reaction was concentrated to dryness, then partitioned between CH2Cl2 and and 50% brine. The organic solution was dried (MgSO4) and concentrated to dry solid. Flash chromatography (5-45% EA/hex, 1% MeOH, 40 g silica) provided 110 mg of 6-(difluoromethoxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile. The material was approximately 80% pure and was used without further purification.

Workup

  1. customThe solution was sparged with argon for 10 min
  2. additionPd(PPh3)4 was added
  3. temperaturethe reaction was heated to 100 C for 2 h
  4. concentrationThe reaction was concentrated to dryness
  5. custompartitioned between CH2Cl2 and and 50% brine
  6. dry with materialThe organic solution was dried (MgSO4)
  7. concentrationconcentrated
  8. customto dry solid

Sources & evidence

ORD record
ord-be1cfeb167a3492fa028a19e70044612
Source dataset
uspto-grants-2010_04
Patent number
US07691879B2

Reaction notes

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