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

HRID 1949630Notes

Reaction equation

HRID 1949630 reaction equation
[C:1]([N:11]([CH3:17])[C@H:12]([C:14]([OH:16])=O)[CH3:13])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[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.[CH2:51]([O:58][C:59]([N:61]1[CH2:65][CH:64]([C:66]2[C:74]3[C:69](=[CH:70][C:71]([F:75])=[CH:72][CH:73]=3)[NH:68][CH:67]=2)[CH:63]2[N:76]([C:79](=[O:89])[CH:80]([NH2:88])[CH:81]([O:83][C:84]([CH3:87])([CH3:86])[CH3:85])[CH3:82])[CH2:77][CH2:78][CH:62]12)=[O:60])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>CN1C(=O)CCC1.CCOC(C)=O>[CH2:51]([O:58][C:59]([N:61]1[CH2:65][CH:64]([C:66]2[C:74]3[C:69](=[CH:70][C:71]([F:75])=[CH:72][CH:73]=3)[NH:68][CH:67]=2)[CH:63]2[N:76]([C:79](=[O:89])[CH:80]([NH:88][C:14](=[O:16])[CH:12]([N:11]([C:1]([O:3][CH2:4][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)=[O:2])[CH3:17])[CH3:13])[CH:81]([O:83][C:84]([CH3:86])([CH3:85])[CH3:87])[CH3:82])[CH2:77][CH2:78][CH:62]12)=[O:60])[C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7016365Z-N-Me-Ala-OHHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674088224-(2-Amino-3-tert-butoxy-butyryl)-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

Product 1

HCID 674091784-{2-[2-(Benzyloxycarbonyl-methyl-amino)-propionylamino]-3-tert-butoxy-butyryl}-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 2

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

Conditions

Temperature
0 °C

Procedure

To a solution containing Cbz-N(Me)Ala-OH (119 mg, 0.5 mmol) in anhydrous NMP (4 mL) was cooled to 0° C. HATU (189 mg, 0.5 mmol) and DIPEA (111 mg, 0.8 mmol) were added followed by the addition of crude 44 (280 mg, 0.5 mmol) in anhydrous NMP (4 mL). The reaction mixture was slowly warmed to ambient temperature. After 2 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 330 mg of crude 45 as an amber-colored oil which was used without further purification. Mass spectrum, m/z [756.4] (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-8f0acc856d804a70b0d6fa62d8e0cb8d
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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