Glycine Hydrochloride → N-(2-Amino-2-oxoethyl)-3-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)benzamide

HRID 1925597Notes

Reaction equation

HRID 1925597 reaction equation
C(N(CC)C(C)C)(C)C.[F:10][C:11]1[CH:12]=[CH:13][C:14]([O:48][CH3:49])=[C:15]([C:17]([CH3:47])([CH3:46])[CH2:18][C:19]([OH:45])([C:41]([F:44])([F:43])[F:42])[CH2:20][NH:21][C:22]2[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]3[C:23]=2[CH:24]=[N:25][N:26]3[C:32]2[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=2)[C:35](O)=[O:36])[CH:16]=1.CN(C(O[N:58]1N=[N:65][C:60]2C=CC=N[C:59]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.NCC(O)=[O:78]>CN(C=O)C>[NH2:58][C:59](=[O:78])[CH2:60][NH:65][C:35](=[O:36])[C:34]1[CH:38]=[CH:39][CH:40]=[C:32]([N:26]2[C:27]3[C:23](=[C:22]([NH:21][CH2:20][C:19]([OH:45])([C:41]([F:44])([F:43])[F:42])[CH2:18][C:17]([C:15]4[CH:16]=[C:11]([F:10])[CH:12]=[CH:13][C:14]=4[O:48][CH3:49])([CH3:46])[CH3:47])[CH:30]=[C:29]([CH3:31])[CH:28]=3)[CH:24]=[N:25]2)[CH:33]=1

Participants

6

Reactant 4

HCID 22316Glycine HydrochlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251807833-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)benzoic acid

Product 1

HCID 24785985N-(2-Amino-2-oxoethyl)-3-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)benzamideYield 81.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N-Diisopropylethylamine (0.109 mL, 0.625 mmol) was added to a solution of 3-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)benzoic acid (70 mg, 0.125 mmol) and HATU (47.5 mg, 0.125 mmol) in DMF (2.5 mL) and the solution stirred at room temperature for 5 min. Glycine hydrochloride (34.6 mg, 0.313 mmol) was added and the mixture stirred at room temperature overnight and then partitioned between 2M HCl (50 mL) and ethyl acetate (50 mL). The organic layer was separated, washed with aqueous sodium bicarbonate (50 ml), dried over anhydrous sodium sulphate and evaporated to give crude product which was purified by mass directed autopreparation (System B) to give the title compound (62.5 mg).

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. custompartitioned between 2M HCl (50 mL) and ethyl acetate (50 mL)
  3. customThe organic layer was separated
  4. washwashed with aqueous sodium bicarbonate (50 ml)
  5. dry with materialdried over anhydrous sodium sulphate
  6. customevaporated
  7. customto give crude product which
  8. customwas purified by mass

Sources & evidence

ORD record
ord-6db2e54089c54ba1bca63a730a1c08a5
Source dataset
uspto-grants-2012_05
Patent number
US08178573B2

Reaction notes

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