Ammonia → N-[(1S)-2-Amino-1-methyl-2-oxoethyl]-3-(4-{[4-[5-fluoro-2-(methloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)-N-methylbenzamide

HRID 1925606Notes

Reaction equation

HRID 1925606 reaction equation
C([N:4](CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:34][C:35]1[CH:36]=[CH:37][C:38]([O:78][CH3:79])=[C:39]([C:41]([CH3:77])([CH3:76])[CH2:42][C:43]([OH:75])([C:71]([F:74])([F:73])[F:72])[CH2:44][NH:45][C:46]2[CH:54]=[C:53]([CH3:55])[CH:52]=[C:51]3[C:47]=2[CH:48]=[N:49][N:50]3[C:56]2[CH:57]=[C:58]([C:62]([N:64]([CH3:70])[C@H:65]([C:67](O)=[O:68])[CH3:66])=[O:63])[CH:59]=[CH:60][CH:61]=2)[CH:40]=1.N.O1CCOCC1>CN(C=O)C.CO>[NH2:4][C:67](=[O:68])[C@@H:65]([N:64]([CH3:70])[C:62](=[O:63])[C:58]1[CH:59]=[CH:60][CH:61]=[C:56]([N:50]2[C:51]3[C:47](=[C:46]([NH:45][CH2:44][C:43]([OH:75])([C:71]([F:74])([F:73])[F:72])[CH2:42][C:41]([C:39]4[CH:40]=[C:35]([F:34])[CH:36]=[CH:37][C:38]=4[O:78][CH3:79])([CH3:77])[CH3:76])[CH:54]=[C:53]([CH3:55])[CH:52]=3)[CH:48]=[N:49]2)[CH:57]=1)[CH3:66]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57672635N-{[3-(4-{[4-[5-Fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)phenyl]carbonyl}-N-methyl-L-alanine

Product 1

HCID 24782917N-[(1S)-2-Amino-1-methyl-2-oxoethyl]-3-(4-{[4-[5-fluoro-2-(methloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)-N-methylbenzamideYield 34.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

N,N-Diisopropylethylamine (0.044 mL, 0.25 mmol) and HATU (20.1 mg, 0.053 mmol) were added to a solution of N-{[3-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)phenyl]carbonyl}-N-methyl-L-alanine (32.4 mg, 0.05 mmol) in DMF (1 mL) and the solution stirred at room temperature under nitrogen for 10 min. Ammonia in dioxan (5M, 1.01 mL, 5.05 mmol) was added and the mixture stirred at room temperature overnight. The mixture was diluted with methanol and purified by mass directed autopreparation (System B) and product containing fractions were partitioned between dichloromethane and aqueous sodium bicarbonate. The organic phase was separated, combined with a second dichloromethane extract, washed twice with water, dried through a hydrophobic frit and evaporated to give the title compound (11 mg).

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. custompurified by mass
  3. additioncontaining fractions
  4. customwere partitioned between dichloromethane and aqueous sodium bicarbonate
  5. customThe organic phase was separated
  6. extractionextract
  7. washwashed twice with water
  8. customdried through a hydrophobic frit
  9. customevaporated

Sources & evidence

ORD record
ord-a0f2547c09f64bc2b25777ab04ea2949
Source dataset
uspto-grants-2012_05
Patent number
US08178573B2

Reaction notes

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