tert-Butyl isocyanate → 1-tert-butyl-3-(2-{(4S)-6-(3-methylphenyl)-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}ethyl)urea

HRID 711416Notes

Reaction equation

HRID 711416 reaction equation
ClC1C=C(C2C=C3C(=O)NCC(CNC(NCC4N5C=C(C6C=CC=C(Cl)C=6)C=C5C(=O)NC4)=O)N3C=2)C=CC=1.Cl.[NH2:42][CH2:43][CH2:44][C@@H:45]1[N:50]2[C:51]([C:65]3[CH:70]=[CH:69][CH:68]=[C:67]([CH3:71])[CH:66]=3)=[C:52]([C:54]3[CH:59]=[CH:58][CH:57]=[C:56]([O:60][C:61]([F:64])([F:63])[F:62])[CH:55]=3)[CH:53]=[C:49]2[C:48](=[O:72])[NH:47][CH2:46]1.[C:73]([N:77]=[C:78]=[O:79])([CH3:76])([CH3:75])[CH3:74].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl.C(OCC)(=O)C>[C:73]([NH:77][C:78]([NH:42][CH2:43][CH2:44][C@@H:45]1[N:50]2[C:51]([C:65]3[CH:70]=[CH:69][CH:68]=[C:67]([CH3:71])[CH:66]=3)=[C:52]([C:54]3[CH:59]=[CH:58][CH:57]=[C:56]([O:60][C:61]([F:64])([F:62])[F:63])[CH:55]=3)[CH:53]=[C:49]2[C:48](=[O:72])[NH:47][CH2:46]1)=[O:79])([CH3:76])([CH3:75])[CH3:74]

Participants

8

Reactant 5

HCID 62412tert-Butyl isocyanateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 867325541,3-Bis{[7-(3-chlorophenyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl]methyl}ureaHCID 86732565(4S)-4-(2-aminoethyl)-6-(3-methylphenyl)-7-[3-(trifluoromethoxy)phenyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one hydrochloride

Product 1

HCID 715232701-tert-butyl-3-(2-{(4S)-6-(3-methylphenyl)-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}ethyl)ureaYield 35%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

28 mg (0.065 mmol) of 1 (4S)-4-(2-aminoethyl)-6-(3-methylphenyl)-7-[3-(trifluoromethoxy)phenyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one hydrochloride were dissolved in 2 ml of DCM. To the obtained solution, 20 μl (0.20 mmol) of t-butyl isocyanate, 60 μl (0.33 mmol) of DIPEA, were added. The mixture was stirred at rt for 18 hours, the solution was portioned between ethyl acetate and saturated aqueous solution of NaHCO3, the organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum. The crude was purified by HPLC preparative method 1, to provide 1-tert-butyl-3-(2-{(4S)-6-(3-methylphenyl)-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}ethyl)urea 12 mg (35%) as a white solid.

Workup

  1. washthe organic layer was washed with brine
  2. dry with materialdried over Na2SO4
  3. customevaporated under vacuum
  4. customThe crude was purified by HPLC preparative method 1

Sources & evidence

ORD record
ord-cecc709c9a7447e98f51d37991161a6c
Source dataset
uspto-grants-2015_11
Patent number
US09181258B2

Reaction notes

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