Diisopropylethylamine → HCID 67505722, compound

HRID 1965211Notes

Reaction equation

HRID 1965211 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([OH:9])=O)[C:3]([CH3:6])([CH3:5])[CH3:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:50]([O:57][C:58]([N:60]1[CH2:64][CH:63]([CH2:65][O:66][C:67]2[CH:72]=[CH:71][C:70]([F:73])=[C:69]([F:74])[CH:68]=2)[CH:62]2[NH:75][CH2:76][CH2:77][CH:61]12)=[O:59])[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>CN1C(=O)CCC1.CCOC(C)=O>[CH2:50]([O:57][C:58]([N:60]1[CH2:64][CH:63]([CH2:65][O:66][C:67]2[CH:72]=[CH:71][C:70]([F:73])=[C:69]([F:74])[CH:68]=2)[CH:62]2[N:75]([C:7](=[O:9])[CH:2]([NH:1][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:3]([CH3:4])([CH3:5])[CH3:6])[CH2:76][CH2:77][CH:61]12)=[O:59])[C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2734668(S)-2-((tert-Butoxycarbonyl)amino)-3,3-dimethylbutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67608196HCID 67608196, compound

Product 1

HCID 67505722HCID 67505722, compoundYield 22.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution of Boc-Tle-OH (463 mg, 2.0 mmol) in NMP (6 mL) was cooled to 0° C. and treated with HATU (758 mg, 2.0 mmol) and DIPEA (0.45 mL, 2.5 mmol). After 10 min, amine 80 (772 mg, 2.0 mmol) in NMP (6 mL) was added. The reaction mixture was allowed to warm to ambient temperature. After 16 h, the solution was diluted with EtOAc, washed successively with 1M HCl, saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was diluted with ACN/water and purified by RP-HPLC (2″ Dynamax® C18, 20% ACN/water to 100% ACN over 30 min; Flow: 40 mL/min). The product-containing fractions were combined, concentrated, and extracted with EtOAc. The organic extract was washed successively with saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, and filtered. The aqueous phase was back-extracted with DCM and the combined organic extracts were concentrated to afford 81 (269 mg) as an off-white foam. 1H NMR (CDCl3, 300 MHz): δ7.37-7.28 (m, 5H), 7.02 (app q, J=9.0 Hz, 1H), 6.66 (m, 1H), 6.52 (m, 1H), 5.28 (d, J=9.6 Hz, 1H), 5.19-5.13 (m, 2H), 4.46 (m, 2H), 4.31 (d, J=9.9 Hz, 1H), 4.01-3.98 (m, 2H), 3.85-3.76 (m, 2H), 3.46-3.37 (m, 2H), 2.81 (app q, J=5.7 Hz, 1H), 2.43 (m, 1H), 2.26 (m, 1H), 1.43 (s, 9H), 0.99 (s, 9H) ppm. Mass spectrum, m/z [602.8] (M+H)+.

Workup

  1. waitAfter 16 h
  2. washwashed successively with 1M HCl, saturated aqueous NaHCO3, and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe residue was diluted with ACN/water
  7. custompurified by RP-HPLC (2″ Dynamax® C18, 20% ACN/water to 100% ACN over 30 min
  8. concentrationconcentrated
  9. extractionextracted with EtOAc
  10. extractionThe organic extract
  11. washwas washed successively with saturated aqueous NaHCO3, and brine
  12. dry with materialdried over anhydrous Na2SO4
  13. filtrationfiltered
  14. extractionThe aqueous phase was back-extracted with DCM
  15. concentrationthe combined organic extracts were concentrated

Sources & evidence

ORD record
ord-163e51a826c543ee8e200171d28c36a4
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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