Triethylamine → N-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(1-hydroxy-1-methylethyl)-1H-indazol-1-yl]methyl}phenyl)methyl]-2-hydroxy-2-methylpropanamide

HRID 1808644Notes

Reaction equation

HRID 1808644 reaction equation
C(N(CC)CC)C.[NH2:8][CH2:9][C:10]1[CH:11]=[C:12]([CH2:16][N:17]2[C:25]3[C:20](=[C:21]([C:26]([OH:29])([CH3:28])[CH3:27])[CH:22]=[CH:23][CH:24]=3)[C:19]([NH:30][S:31]([C:34]3[S:35][C:36]([Cl:39])=[CH:37][CH:38]=3)(=[O:33])=[O:32])=[N:18]2)[CH:13]=[CH:14][CH:15]=1.C([O:43][C:44]([CH3:49])([CH3:48])[C:45](Cl)=[O:46])(=O)C.C(=O)([O-])[O-].[K+].[K+]>ClCCl.CS(C)=O.CO>[Cl:39][C:36]1[S:35][C:34]([S:31]([NH:30][C:19]2[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([OH:29])([CH3:27])[CH3:28])[N:17]([CH2:16][C:12]3[CH:11]=[C:10]([CH2:9][NH:8][C:45](=[O:46])[C:44]([OH:43])([CH3:49])[CH3:48])[CH:15]=[CH:14][CH:13]=3)[N:18]=2)(=[O:33])=[O:32])=[CH:38][CH:37]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 1234962-Acetoxyisobutyroyl chlorideHCID 59456043N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(1-hydroxy-1-methylethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

Product 1

HCID 59456035N-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(1-hydroxy-1-methylethyl)-1H-indazol-1-yl]methyl}phenyl)methyl]-2-hydroxy-2-methylpropanamideYield 24%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (0.034 mL, 0.244 mmol) was added to N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(1-hydroxy-1-methylethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide (for a preparation see Intermediate 78) (40 mg, 0.081 mmol) in dichloromethane (1 mL). 2-Chloro-1,1-dimethyl-2-oxoethyl acetate (0.013 mL, 0.090 mmol) was added and the reaction mixture was stirred at room temp for 2 h. The reaction mixture was concentrated on the blowdown, potassium carbonate (113 mg, 0.815 mmol) and methanol (2 mL) was added and the reaction was stirred at room temp for 1 h. LCMS showed the acetate group was removed. The reaction mixture was concentrated, acidified with 2N HCl and extracted with EtOAc (2×15 mL). The combined organic layers were dried by passing through a hydrophobic frit and concentrated to afford the crude product as a yellow oil. The residue was dissolved in DMSO (1 mL) and purified by Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a Formic acid modifier (Method A). The solvent was removed under a stream of nitrogen in the Radleys blowdown apparatus to give the title compound (11.5 mg, 24%). LCMS (System A) RT=1.05 min, ES+ve m/z 577/579 (M+H)+.

Workup

  1. additionwas added
  2. stirringthe reaction was stirred at room temp for 1 h
  3. customwas removed
  4. concentrationThe reaction mixture was concentrated
  5. extractionextracted with EtOAc (2×15 mL)
  6. customThe combined organic layers were dried
  7. concentrationconcentrated
  8. customto afford the crude product as a yellow oil
  9. custompurified by Mass Directed AutoPrep on Sunfire C18 column
  10. customThe solvent was removed under a stream of nitrogen in the Radleys blowdown apparatus

Sources & evidence

ORD record
ord-ff9098a34c6e4160a6040beed68f1e13
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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