Diisopropylethylamine → 4-(3-tert-Butoxy-2-tert-butoxycarbonylamino-butyryl)-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

HRID 1949628Notes

Reaction equation

HRID 1949628 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=O)[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].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.[CH2:53]([O:60][C:61]([N:63]1[CH2:67][CH:66]([C:68]2[C:76]3[C:71](=[CH:72][C:73]([F:77])=[CH:74][CH:75]=3)[NH:70][CH:69]=2)[CH:65]2[NH:78][CH2:79][CH2:80][CH:64]12)=[O:62])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1>CN1C(=O)CCC1.CCOC(C)=O>[CH2:53]([O:60][C:61]([N:63]1[CH2:67][CH:66]([C:68]2[C:76]3[C:71](=[CH:72][C:73]([F:77])=[CH:74][CH:75]=3)[NH:70][CH:69]=2)[CH:65]2[N:78]([C:10](=[O:12])[CH:2]([NH:1][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:3]([O:4][C:5]([CH3:6])([CH3:7])[CH3:8])[CH3:9])[CH2:79][CH2:80][CH:64]12)=[O:62])[C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7015770(2S,3R)-3-(tert-butoxy)-2-(((tert-butoxy)carbonyl)amino)butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672129273-(6-Fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

Product 1

HCID 674094014-(3-tert-Butoxy-2-tert-butoxycarbonylamino-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 Boc-Thr(tBu)-OH (138 mg, 0.5 mmol) in anhydrous NMP (4 mL) was cooled to 0° C. HATU (190 mg, 0.5 mmol) and DIPEA (111 mg, 0.8 mmol) were added followed by the addition of crude 42 (195 mg, 0.5 mmol) in anhydrous NMP (5 mL). The reaction mixture was slowly warmed to ambient temperature. After 4 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 336 mg of crude 43 as an amber-colored foam which was used without further purification. Mass spectrum, m/z [637.3] (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-e445000a52c04e2caa3302d6776f8c30
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

Loading…