Triethylamine → HCID 58054468, compound

HRID 1892970Notes

Reaction equation

HRID 1892970 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[C:15]([O:20][CH3:21])[CH:16]=[CH:17][CH:18]=3)[C:13]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:12]2)[CH:7]=[CH:8][CH:9]=1.C(N(CC)CC)C.C([O:42][C@@H:43]([CH3:47])[C:44](Cl)=[O:45])(=O)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[Cl:31][C:28]1[S:27][C:26]([S:23]([NH:22][C:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH3:21])[N:11]([CH2:10][C:6]3[CH:5]=[C:4]([CH2:3][NH:2][C:44](=[O:45])[C@@H:43]([OH:42])[CH3:47])[CH:9]=[CH:8][CH:7]=3)[N:12]=2)(=[O:25])=[O:24])=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 66632476N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride

Product 1

HCID 58054468HCID 58054468, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride (for a preparation see Intermediate 4) (100 mg, 0.2 mmol) in DCM (5 mL) and triethylamine (0.28 mL, 2 mmol) was treated with the (S)-2-acetoxypropionyl chloride (0.065 mL). After 4 h, the solvent was removed by evaporation and the residue was dissolved in methanol (10 mL) and then treated with solid potassium carbonate (277 mg, 2 mmol) and the mixture was stood at RT for 3 days. The mixture was concentrated under reduced pressure, and the residue was partitioned between 2M HCl and ethyl acetate. The organic solution was washed with more HCl, brine and dried (MgSO4). The filtrate was evaporated under reduced pressure to give a white solid (113 mg). The sample was dissolved in 1:1 MeOH-DMSO 2 mL and purified by Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a Formic acid modifier (Method A). The solvent was evaporated in vacuo to give the title compound (86 mg, 80%): LCMS (System A) RT=0.97 min, 100%, ES+ve m/z 535/537 (M+H)+; NMR δ (CD3OD) 7.27-7.15 (5H, m), 7.05 (1H, br d, J=7 Hz), 6.97 (1H, d, J=8 Hz), 6.89 (1H, d, J 4 Hz), 6.42 (1H, d, J=8 Hz), 5.47 (2H, s), 4.33 (2H, s), 4.12 (1H, q, J=7 Hz), 3.76 (3H, s), 1.30 (3H, d, J=7 Hz).

Workup

  1. customthe solvent was removed by evaporation
  2. dissolutionthe residue was dissolved in methanol (10 mL)
  3. waitthe mixture was stood at RT for 3 days
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customthe residue was partitioned between 2M HCl and ethyl acetate
  6. washThe organic solution was washed with more HCl, brine
  7. dry with materialdried (MgSO4)
  8. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-723f16372ff442f086ecff2f0efdd192
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

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