Methanol → HCID 68860780, compound

HRID 857508Notes

Reaction equation

HRID 857508 reaction equation
F[B-](F)(F)F.F[B-](F)(F)F.ClC[N+]12CC[N+]([F:21])(CC1)CC2.[C:22]([O:26][C:27](=[O:44])[C:28]1[C:33]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([Br:41])=[CH:37][C:36]=2[Cl:42])=[CH:32][C:31]([NH2:43])=[N:30][CH:29]=1)([CH3:25])([CH3:24])[CH3:23].CO>CCOC(C)=O.O>[C:22]([O:26][C:27](=[O:44])[C:28]1[C:33]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([Br:41])=[CH:37][C:36]=2[Cl:42])=[C:32]([F:21])[C:31]([NH2:43])=[N:30][CH:29]=1)([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 3

HCID 887MethanolHCID 2724933SelectfluorHCID 68859908HCID 68859908, compound

Product 1

HCID 68860780HCID 68860780, compoundYield 7.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (889 mg, 2.508 mmol) was added to a mixture of 6-amino-4-(4-bromo-2-chlorophenylamino)nicotinic acid tert-butyl ester (42) (1.00 g, 2.51 mmol) in 1:1 MeOH:water (25 mL). After about 2 hours, the reaction mixture was diluted with EtOAc and water. The layers were separated and the organic layer washed with 0.5 N HCl and brine. The aqueous washes were back extracted with EtOAc. The combined organic extracts were dried (Na2SO4) and concentrated. Purification by flash column chromatography using the Biotage system (20:1 hexanes:EtOAc to 15:1 hexanes:EtOAc) provided the desired product (45) as a yellow solid (75 mg, 7%).

Workup

  1. customThe layers were separated
  2. washthe organic layer washed with 0.5 N HCl and brine
  3. extractionThe aqueous washes were back extracted with EtOAc
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-d2463bb3cee545a79177836033ac94f4
Source dataset
uspto-grants-2006_12
Patent number
US07144907B2

Reaction notes

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