Acetic Acid → HCID 59456019, compound

HRID 1874740Notes

Reaction equation

HRID 1874740 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[C:14]([O:20][CH3:21])[C:15]([F:19])=[CH:16][CH:17]=3)[C:12]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:11]2)[CH:6]=[CH:7][CH:8]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:65](O)(=[O:67])[CH3:66]>CN(C=O)C.CO.CS(C)=O>[Cl:31][C:28]1[S:27][C:26]([S:23]([NH:22][C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[O:20][CH3:21])[N:10]([CH2:9][C:5]3[CH:4]=[C:3]([CH2:2][NH:1][C:65](=[O:67])[CH3:66])[CH:8]=[CH:7][CH:6]=3)[N:11]=2)(=[O:25])=[O:24])=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59455989N-[1-{[3-(Aminomethyl)phenyl]methyl}-5-fluoro-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

Product 1

HCID 59456019HCID 59456019, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

A solution of N-[1-{[3-(aminomethyl)phenyl]methyl}-5-fluoro-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide (for a preparation see Intermediate 61) (49 mg, 0.10 mmol) in dry DMF (4 mL) was treated with HATU (38.7 mg, 0.10 mmol) and stirred under nitrogen for 3 min prior to the addition of DIPEA (0.018 mL, 0.10 mmol). The reaction mixture was stirred for a further 3 min prior to the addition of acetic acid (6.12 mg, 0.10 mmol) and stirring continued for a further 3 h. The reaction mixture was concentrated by nitrogen in a blowdown unit and the sample was loaded in dichloromethane onto aminopropyl ion-exchange cartridge (1 g) pre-equilibrated with DCM. The sample was eluted with methanol/dichloromethane and dried under a stream of nitrogen in the Radleys blowdown apparatus to give the crude product. The sample was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier (Method C). The solvent was evaporated in vacuo using the Genevac to give the title compound (14.5 mg, 27%): LCMS (System A) RT=1.06 min, ES+ve m/z 523/525 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred for a further 3 min
  2. stirringstirring
  3. waitcontinued for a further 3 h
  4. concentrationThe reaction mixture was concentrated by nitrogen in a blowdown unit
  5. washThe sample was eluted with methanol/dichloromethane
  6. customdried under a stream of nitrogen in the Radleys blowdown apparatus
  7. customto give the crude product
  8. custompurified by Mass Directed AutoPrep on Xbridge column
  9. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-f30377e2e60d49659ef2608324680c54
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

Loading…