Hydrochloric Acid → HCID 86610168, compound

HRID 1510164Notes

Reaction equation

HRID 1510164 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:8]2[C@@:12]3([CH2:17][CH2:16][N:15]([CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21](I)[CH:20]=4)[C@@H:14]([CH3:26])[CH2:13]3)[C:11]([NH:27][CH3:28])=[N:10][C:9]2=[O:29])[CH:5]=[CH:6][CH:7]=1.[C:30]1([CH3:39])[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1B(O)O.C([O-])([O-])=O.[K+].[K+].[ClH:46]>>[Cl-:46].[Cl-:46].[F:1][C:2]1[CH:3]=[C:4]([N:8]2[C@@:12]3([CH2:17][CH2:16][NH+:15]([CH2:18][C:19]4[CH:20]=[C:21]([C:31]5[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=5[CH3:39])[CH:22]=[CH:23][CH:24]=4)[C@@H:14]([CH3:26])[CH2:13]3)[C:11]([NH2+:27][CH3:28])=[N:10][C:9]2=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 178482456HCID 178482456, compound

Product 1

HCID 86610168HCID 86610168, compound

Conditions

Temperature
120 °C

Procedure

A Biotage microwave vial was charged with intermediate (5R,7S)-1-(3-fluorophenyl)-8-(3-iodobenzyl)-7-methyl-4-(methylamino)-1,3,8-triazaspiro[4.5]dec-3-en-2-one (60 mg, 0.118 mmol) from step 3 above, PdCl2dppf (4.3 mg, 0.01 mmol) and 2-tolylboronic acid (21 mg, 0.15 mmol). The vial was sealed and put under a nitrogen atmosphere. To the solids was added aqueous 1.5M K2CO3 (0.24 mL, 0.35 mmol) and degassed THF (0.7 mL). The mixture was briefly vortexed and heated in an Optimizer microwave for 5 min. at 120° C. The reaction enclosure was removed and the reaction diluted with EtOAc and water. The organic layer was washed with brine, dried over Na2SO4 and the solvent removed under reduce pressure. Purification over silica via automated flash chromatography (0 to 10% MeOH/CH2Cl2) afforded, after solvent removal under reduced pressure, the product as a white solid. The salt was prepared by mixing the free base with ethereal HCl and evaporating to give the product as a solid.

Workup

  1. customThe vial was sealed
  2. customdegassed THF (0.7 mL)
  3. customThe reaction enclosure was removed
  4. additionthe reaction diluted with EtOAc and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent removed
  8. customPurification over silica via automated flash chromatography (0 to 10% MeOH/CH2Cl2)
  9. customafforded
  10. customafter solvent removal under reduced pressure
  11. customThe salt was prepared
  12. customevaporating

Sources & evidence

ORD record
ord-524e51de82ee42f791262a9d9ae7d1e8
Source dataset
uspto-grants-2012_07
Patent number
US08211904B2

Reaction notes

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