Hydrochloric Acid → HCID 58697321, compound

HRID 2212726Notes

Reaction equation

HRID 2212726 reaction equation
F[C:2]1[N:28]=[CH:27][CH:26]=[CH:25][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[C:9]([O:17][CH2:18][CH:19]2[CH2:23][CH2:22][CH2:21][N:20]2[CH3:24])[CH:8]=1)=[O:5].C(O)(C(F)(F)F)=O.[NH2:36][C:37]1[CH:45]=[CH:44][CH:43]=[C:42]2[C:38]=1[CH2:39][NH:40][C:41]2=[O:46].Cl.[OH-].[Na+]>C(O)(C)(C)C>[CH3:24][N:20]1[CH2:21][CH2:22][CH2:23][C@@H:19]1[CH2:18][O:17][C:9]1[CH:8]=[C:7]([NH:6][C:4]([C:3]2[C:2]([NH:36][C:37]3[CH:45]=[CH:44][CH:43]=[C:42]4[C:38]=3[CH2:39][NH:40][C:41]4=[O:46])=[N:28][CH:27]=[CH:26][CH:25]=2)=[O:5])[CH:12]=[CH:11][C:10]=1[C:13]([F:16])([F:15])[F:14]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 98555134-AMINOISOINDOLIN-1-ONEHCID 69439673HCID 69439673, compound

Product 1

HCID 58697321HCID 58697321, compound

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
150 °C

Procedure

2-Fluoro-N-[3-(1-methyl-pyrrolidin-2-ylmethoxy)-4-trifluoromethyl-phenyl]-nicotinamide (402 mg, 1.0116 mmol) was dissolved in tert-butanol (1 mL). To this mix was added TFA (115 mg, 1.0116 mmol) and 4-amino-2,3-dihydro-isoindol-1-one (450 mg, 3.035 mmol). The mix was heated for 6 h at 150° C., allowing the solvent to boil off. The reaction was cooled to RT, dissolved into 1N aqueous HCl, basified to pH 10 with solid NaOH, extracted twice with EtOAc, and dried over Na2SO4. The product precipitated out of solution along with a minor by-product. The EtOAc was filtered off. The crude product was dissolved in MeOH and filtered. The MeOH solution was concentrated down and eluted on silica gel column to yield the titled compound as a light yellow solid. MS: C27H26F3N5O3—525.528; M+H 526.1

Workup

  1. temperatureThe reaction was cooled to RT
  2. extractionextracted twice with EtOAc
  3. dry with materialdried over Na2SO4
  4. customThe product precipitated out of solution along with a minor by-product
  5. filtrationThe EtOAc was filtered off
  6. dissolutionThe crude product was dissolved in MeOH
  7. filtrationfiltered
  8. concentrationThe MeOH solution was concentrated down
  9. washeluted on silica gel column

Sources & evidence

ORD record
ord-be0cecb6f8e9486683bc1d53fa63bebe
Source dataset
uspto-grants-2006_09
Patent number
US07102009B2

Reaction notes

Loading…