Hydrochloric Acid → HCID 71164602, compound

HRID 1182294Notes

Reaction equation

HRID 1182294 reaction equation
[F:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C@@H:10]([C@@H:12]([NH:17]C(=O)OC(C)(C)C)[CH2:13][CH2:14][CH2:15][CH3:16])[OH:11])[CH:5]=[CH:4][CH:3]=1.FC1N=C(NC[C@H]([C@@H](NC(=O)OC(C)(C)C)CCCC)O)C=CC=1.Cl.C(N(CC)C(C)C)(C)C.[C:59](=[O:92])(OC1C=CC([N+]([O-])=O)=CC=1)[O:60][C@H:61]([CH2:66][N:67]1[CH:71]=[CH:70][C:69]([C:72]2[CH:77]=[CH:76][C:75]([C:78]([F:81])([F:80])[F:79])=[CH:74][CH:73]=2)=[N:68]1)[C:62]([CH3:65])([CH3:64])[CH3:63]>O1CCOCC1.CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C@@H:10]([C@@H:12]([NH:17][C:59](=[O:92])[O:60][C@H:61]([CH2:66][N:67]2[CH:71]=[CH:70][C:69]([C:72]3[CH:73]=[CH:74][C:75]([C:78]([F:80])([F:79])[F:81])=[CH:76][CH:77]=3)=[N:68]2)[C:62]([CH3:63])([CH3:65])[CH3:64])[CH2:13][CH2:14][CH2:15][CH3:16])[OH:11])[CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 58981715HCID 58981715, compoundHCID 58981758HCID 58981758, compoundHCID 69512678HCID 69512678, compound

Product 1

HCID 71164602HCID 71164602, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 40 mg (0.12 mmol) of tert-butyl (1S)-1-{(1S)-2-[(6-fluoro-2-pyridinyl)amino]-1-hydroxyethyl}pentylcarbamate & tert-butyl (1S)-1-{(1R)-2-[(6-fluoro-2-pyridinyl)amino]-1-hydroxyethyl}pentylcarbamate in 1 mL dioxane was added 5 mL of 4M hydrochloric acid in dioxane. The reaction mixture was stirred for 2 h before being concentrated under reduced pressure. The residue was dissolved in 1 mL of N,N-dimethylformamide before 0.081 mL (0.47 mmol) of N,N-diisopropylethylamine and 56 mg (0.12 mmol) of (1S)-2,2-dimethyl-1-({3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl 4-nitrophenyl carbonate were added. The reaction mixture was stirred at room temperature for 18 h, diluted with ethyl acetate, washed with 1M sodium hydroxide and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with ethyl acetate:hexanes (2:3) to afford 40 mg (59%) of (1S)-2,2-dimethyl-1-({3-[4(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl (1S)-1-{(1S)-2-[(6-fluoro-2-pyridinyl)amino]-1-hydroxyethyl}pentylcarbamate & (1S)-2,2-dimethyl-1-({3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl (1S)-1-{(1R)-2-[(6-fluoro-2-pyridinyl)amino]-1-hydroxyethyl}pentylcarbamate. ES-LCMS m/z 602 (M+Na).

Workup

  1. concentrationbefore being concentrated under reduced pressure
  2. additionwere added
  3. stirringThe reaction mixture was stirred at room temperature for 18 h
  4. washwashed with 1M sodium hydroxide and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with ethyl acetate:hexanes (2:3)

Sources & evidence

ORD record
ord-2188b2070cc2493999b71cfd92cc06a5
Source dataset
uspto-grants-2007_10
Patent number
US07288541B2

Reaction notes

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