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

HRID 1874727Notes

Reaction equation

HRID 1874727 reaction equation
C(O)=O.[NH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][N:13]2[C:21]3[C:16](=[C:17]([O:22][CH3:23])[CH:18]=[CH:19][CH:20]=3)[C:15]([NH:24][S:25]([C:28]3[S:29][C:30]([Cl:33])=[CH:31][CH:32]=3)(=[O:27])=[O:26])=[N:14]2)=[CH:8][CH:7]=1.[C:34](O)(=[O:36])[CH3:35].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C.C(Cl)Cl.O>[Cl:33][C:30]1[S:29][C:28]([S:25]([NH:24][C:15]2[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][C:17]=3[O:22][CH3:23])[N:13]([CH2:12][C:9]3[CH:8]=[CH:7][C:6]([CH2:5][NH:4][C:34](=[O:36])[CH3:35])=[CH:11][CH:10]=3)[N:14]=2)(=[O:27])=[O:26])=[CH:32][CH:31]=1

Participants

8

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 66632574n-[1-{[4-(Aminomethyl)phenyl]methyl}-4-(methyloxy)-1h-indazol-3-yl]-5-chloro-2-thiophenesulfonamide formate salt

Product 1

HCID 58054491N-[(4-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]acetamideYield 87%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of N-[1-{[4-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide formate salt for a preparation see Intermediate 30) (15 mg, 0.03 mmol) and acetic acid (0.001 mL, 0.03 mmol) in acetonitrile (2 mL) and DIPEA (0.046 mL, 0.26 mmol) was treated with HATU (37.0 mg, 0.097 mmol) and the resulting mixture was stirred for 2 h and 15 min at ambient temperature. The reaction mixture was diluted with DCM (2 mL) and water (3 mL). The organic was separated and the aqueous layer was further extracted with DCM (2 mL). The combined organic solutions were dried through an hydrophobic frit and concentrated under reduced pressure. The residue was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on (supelcosil ABZ+Plus column) eluting with solvents A/B (A: Water+0.1% Formic acid, B: MeCN:Water 95:5+0.05% Formic acid). The solvent was removed under a stream of nitrogen in a Radleys blowdown apparatus to give the title compound (13 mg, 87%) as a gum. LCMS (System A) RT=1.11 min, ES+ve m/z 505/507 (M+H)+.

Workup

  1. customThe organic was separated
  2. extractionthe aqueous layer was further extracted with DCM (2 mL)
  3. customThe combined organic solutions were dried through an hydrophobic frit
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in 1:1 MeOH-DMSO (1 mL)
  6. custompurified by Mass Directed AutoPrep on (supelcosil ABZ+Plus column)
  7. washeluting with solvents A/B (A: Water+0.1% Formic acid, B
  8. customThe solvent was removed under a stream of nitrogen in a Radleys blowdown apparatus

Sources & evidence

ORD record
ord-93b54f5e138943518b2275a0cf9f3de0
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

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