Hydrochloric Acid → (3r)-n-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(1-hydroxyethyl)-1h-indazol-1-yl]methyl}phenyl)methyl]-3-morpholinecarboxamide formate salt

HRID 1808643Notes

Reaction equation

HRID 1808643 reaction equation
CCN(C(C)C)C(C)C.CC([O:14][C:15]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]1[C:23]([OH:25])=O)=[O:16])(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:50][CH2:51][C:52]1[CH:53]=[C:54]([CH2:58][N:59]2[C:67]3[C:62](=[C:63]([CH:68]([OH:70])[CH3:69])[CH:64]=[CH:65][CH:66]=3)[C:61]([NH:71][S:72]([C:75]3[S:76][C:77]([Cl:80])=[CH:78][CH:79]=3)(=[O:74])=[O:73])=[N:60]2)[CH:55]=[CH:56][CH:57]=1.Cl.O1CCOCC1>C(Cl)Cl>[CH:15]([OH:16])=[O:14].[Cl:80][C:77]1[S:76][C:75]([S:72]([NH:71][C:61]2[C:62]3[C:67](=[CH:66][CH:65]=[CH:64][C:63]=3[CH:68]([OH:70])[CH3:69])[N:59]([CH2:58][C:54]3[CH:53]=[C:52]([CH2:51][NH:50][C:23]([C@H:18]4[CH2:19][O:20][CH2:21][CH2:22][NH:17]4)=[O:25])[CH:57]=[CH:56][CH:55]=3)[N:60]=2)(=[O:73])=[O:74])=[CH:79][CH:78]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 1512538(3R)-4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59456025N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(1-hydroxyethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

Product 1

HCID 66664627(3r)-n-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(1-hydroxyethyl)-1h-indazol-1-yl]methyl}phenyl)methyl]-3-morpholinecarboxamide formate saltYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIPEA (0.059 mL, 0.336 mmol) was added to a stirring solution of (3R)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-morpholinecarboxylic acid (19.41 mg, 0.084 mmol) in DCM (1 mL). HATU (35.1 mg, 0.092 mmol) was then added followed by N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(1-hydroxyethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide (for a preparation see Intermediate 77) (44 mg, 0.084 mmol) and stirred for an hour at room temp. The mixture was treated with 4M hydrogen chloride in dioxane (0.5 mL, 2 mmol) and the reaction stirred at room temperature for 0.5 h. The reaction mixture was passed through an SCX-2 cartridge, washed with methanol and then eluted using 2M ammonia in methanol. The appropriate ammoniacal fractions were concentrated under reduced pressure and the residue was dissolved in DMSO-Methanol (1:1) (1 mL) and purified by MDAP (Method A) to give the title compound (31.2 mg, 58%). LCMS (System C) RT=2.04 min, ES+ve m/z 590/592 (M+H)+.

Workup

  1. stirringthe reaction stirred at room temperature for 0.5 h
  2. washwashed with methanol
  3. washeluted
  4. concentrationThe appropriate ammoniacal fractions were concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in DMSO-Methanol (1:1) (1 mL)
  6. custompurified by MDAP (Method A)

Sources & evidence

ORD record
ord-fa58d93299714980a46cb688f04434f4
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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