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

HRID 1892957Notes

Reaction equation

HRID 1892957 reaction equation
N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[C:25]([OH:28])(=O)[CH3:26].C(N(CC)C(C)C)(C)C.C(O)=O.[NH2:41][CH2:42][C:43]1[CH:44]=[C:45]([CH2:49][N:50]2[C:58]3[C:53](=[C:54]([OH:59])[CH:55]=[CH:56][CH:57]=3)[C:52]([NH:60][S:61]([C:64]3[S:65][C:66]([Cl:69])=[CH:67][CH:68]=3)(=[O:63])=[O:62])=[N:51]2)[CH:46]=[CH:47][CH:48]=1>CN(C=O)C>[Cl:69][C:66]1[S:65][C:64]([S:61]([NH:60][C:52]2[C:53]3[C:58](=[CH:57][CH:56]=[CH:55][C:54]=3[OH:59])[N:50]([CH2:49][C:45]3[CH:44]=[C:43]([CH2:42][NH:41][C:25](=[O:28])[CH3:26])[CH:48]=[CH:47][CH:46]=3)[N:51]=2)(=[O:62])=[O:63])=[CH:68][CH:67]=1

Participants

6

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 136346357n-(1-{[3-(Aminomethyl)phenyl]methyl}-4-hydroxy-1h-indazol-3-yl)-5-chloro-2-thiophenesulfonamide formate salt

Product 1

HCID 136116031N-({3-[(3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-hydroxy-1H-indazol-1-yl)methyl]phenyl}methyl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (39.7 mg, 0.064 mmol) in anhydrous DMF (1 mL) was added at room temperature acetic acid (3.36 μL, 0.059 mmol), followed by N,N-diisopropylethylamine (0.031 mL, 0.18 mmol) and finally a solution of N-(1-{[3-(aminomethyl)phenyl]methyl}-4-hydroxy-1H-indazol-3-yl)-5-chloro-2-thiophenesulfonamide formate salt (for a preparation see Intermediate 15) (29 mg, 0.059 mmol) in anhydrous DMF (1 mL) and the reaction mixture was stirred at room temperature for 30 min. The mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer was separated, washed with brine:water (1:1), passed through a hydrophobic frit and evaporated in-vacuo to yield a colourless oil (23 mg). This was dissolved in MeOH:DMSO (1 mL) and purified by MDAP Sunfire C18 column eluting with solvents A/B (A: 0.1% v/v solution of formic acid in water, B: 0.1% v/v solution of formic acid in acetonitrile) (25 min run). The appropriate fraction was evaporated in-vacuo to yield the title compound as a colourless oil (20 mg, 69%). LCMS (System B) RT=2.41 min, ES+ve m/z 491/493 (M+H)+.

Workup

  1. customThe mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine:water (1:1)
  4. customevaporated in-vacuo

Sources & evidence

ORD record
ord-b71e32e73ad1424289bd15edc1fa433f
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

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