Hydrochloric Acid → HCID 69512887, compound

HRID 1182291Notes

Reaction equation

HRID 1182291 reaction equation
[OH:1][C@H:2]([C@@H:13]([NH:18]C(=O)OC(C)(C)C)[CH2:14][CH2:15][CH2:16][CH3:17])[CH2:3][NH:4][C:5]([N:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1)=[O:6].O[C@@H]([C@@H](NC(=O)OC(C)(C)C)CCCC)CNC(N1CCOCC1)=O.Cl.C(N(CC)C(C)C)(C)C.[C:61](=[O:94])(OC1C=CC([N+]([O-])=O)=CC=1)[O:62][C@H:63]([CH2:68][N:69]1[CH:73]=[CH:72][C:71]([C:74]2[CH:79]=[CH:78][C:77]([C:80]([F:83])([F:82])[F:81])=[CH:76][CH:75]=2)=[N:70]1)[C:64]([CH3:67])([CH3:66])[CH3:65]>O1CCOCC1.CN(C)C=O.C(OCC)(=O)C>[OH:1][C@H:2]([C@@H:13]([NH:18][C:61](=[O:94])[O:62][C@H:63]([CH2:68][N:69]1[CH:73]=[CH:72][C:71]([C:74]2[CH:79]=[CH:78][C:77]([C:80]([F:81])([F:83])[F:82])=[CH:76][CH:75]=2)=[N:70]1)[C:64]([CH3:66])([CH3:65])[CH3:67])[CH2:14][CH2:15][CH2:16][CH3:17])[CH2:3][NH:4][C:5]([N:7]1[CH2:8][CH2:9][O:10][CH2:11][CH2:12]1)=[O:6]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 58981734HCID 58981734, compoundHCID 58981760HCID 58981760, compoundHCID 69512678HCID 69512678, compound

Product 1

HCID 69512887HCID 69512887, compoundYield 55.8%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 130 mg (0.36 mmol) of tert-butyl (1S)-1-{(1S)-1-hydroxy-2-[(4-morpholinylcarbonyl)amino]ethyl}pentylcarbamate & tert-butyl (1S)-1-{(1R)-1-hydroxy-2-[(4-morpholinylcarbonyl)amino]ethyl}pentylcarbamate in 1 mL of dioxane was added 5 mL of 4M hydrochloric acid in dioxane. The reaction mixture was stirred for 2 h and concentrated under reduced pressure. Half of the product was carried forward. This material was slurried in N,N-dimethylformamide before 0.094 mL (0.54 mmol) of N,N-diisopropylethylamine was added, followed by 86 mg (0.18 mmol) of (1S)-2,2-dimethyl-1-({3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl 4-nitrophenyl carbonate. The reaction mixture was stirred at room temperature for 18 h, and then diluted with ethyl acetate before being 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 to afford 60 mg (55%) of (1S)-2,2-dimethyl-1-({3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl (1S)-1-{(1S)-1-hydroxy-2-[(4-morpholinylcarbonyl)amino]ethyl}pentylcarbamate & (1S)-2,2-dimethyl-1-({3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl (1S)-1-{(1R)-1-hydroxy-2-[(4-morpholinylcarbonyl)amino]ethyl}pentylcarbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.99 (m, 2H), 7.74 (d, J=8 Hz, 2H), 6.77 (s, 1H), 6.58 (d, J=9 Hz, 1H), 6.33 (m, 1H), 4.95–4.75 (m, 2H), 4.48 (d, J=13 Hz, 1H), 4.19 (t, J=12 Hz, 1H), 3.45–3.10 (m, 13H), 1.25 (m, 1H), 0.99 (m, 14H), 0.67 (m, 3H); ES-LCMS m/z 620 (M+Na).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionwas added
  3. stirringThe reaction mixture was stirred at room temperature for 18 h
  4. washbefore being washed 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

Sources & evidence

ORD record
ord-6603288ed0ab47eab2717eae4d593276
Source dataset
uspto-grants-2007_10
Patent number
US07288541B2

Reaction notes

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