Diisopropylethylamine → 4-{2-[2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid methyl ester

HRID 1949636Notes

Reaction equation

HRID 1949636 reaction equation
[C:1]([N:8]([CH3:14])[C@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].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.[CH3:48][O:49][C:50]([N:52]1[CH2:56][CH:55]([C:57]2[C:65]3[C:60](=[CH:61][C:62]([F:66])=[CH:63][CH:64]=3)[NH:59][CH:58]=2)[CH:54]2[N:67]([C:70](=[O:79])[CH:71]([NH2:78])[CH:72]3[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]3)[CH2:68][CH2:69][CH:53]12)=[O:51]>CN1C(=O)CCC1.CCOC(C)=O>[CH3:48][O:49][C:50]([N:52]1[CH2:56][CH:55]([C:57]2[C:65]3[C:60](=[CH:61][C:62]([F:66])=[CH:63][CH:64]=3)[NH:59][CH:58]=2)[CH:54]2[N:67]([C:70](=[O:79])[CH:71]([NH:78][C:11](=[O:13])[CH:9]([N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH3:14])[CH3:10])[CH:72]3[CH2:73][CH2:74][CH2:75][CH2:76][CH2:77]3)[CH2:68][CH2:69][CH:53]12)=[O:51]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67213375HCID 67213375, compound

Product 1

HCID 674113594-{2-[2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

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

Conditions

Temperature
0 °C

Procedure

To a solution containing Boc-N(Me)Ala-OH (76 mg, 0.37 mmol) in anhydrous NMP (4 mL) was cooled to 0° C. HATU (141 mg, 0.37 mmol) and DIPEA (148 mg, 1.14 mmol) were added followed by the addition of crude 51 (172 mg, 0.39 mmol) in anhydrous NMP (5 mL). The reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with EtOAc and washed successively with 1M HCl, aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 255 mg of crude 52 as an off-white-colored foam which was used without further purification. Mass spectrum, m/z [628.5] (M+H)+.

Workup

  1. temperatureThe reaction mixture was slowly warmed to ambient temperature
  2. washwashed successively with 1M HCl, aqueous NaHCO3, and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c7ce3fdb14f14e94993369d0ecfb5996
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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