Diisopropylethylamine → 4-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-3-phenylcarbamoyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

HRID 446976Notes

Reaction equation

HRID 446976 reaction equation
[NH:1]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C@H:2]([C:9]([OH:11])=O)[CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.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.[CH2:52]([O:59][C:60]([N:62]1[CH2:66][CH:65]([C:67](=[O:75])[NH:68][C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[CH:64]2[NH:76][CH2:77][CH2:78][CH:63]12)=[O:61])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>CN1C(=O)CCC1.CCOCC>[CH2:52]([O:59][C:60]([N:62]1[CH2:66][CH:65]([C:67](=[O:75])[NH:68][C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=2)[CH:64]2[N:76]([C:9](=[O:11])[CH:2]([NH:1][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:3]3[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]3)[CH2:77][CH2:78][CH:63]12)=[O:61])[C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67281286HCID 67281286, compound

Product 1

HCID 672814864-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-3-phenylcarbamoyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl esterYield 92.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of Boc-Chg-OH (222 mg, 0.86 mmol) in NMP (5 mL) was cooled to 0° C. and treated with HATU (328 mg, 0.86 mmol) and DIPEA (0.17 mL, 0.98 mmol) followed, in 15 min, by the addition of 38 (300 mg, 0.82 mmol). The reaction mixture was allowed to warm to ambient temperature. After 18 h, the solution was diluted with Et2O, washed with H2O, 1M HCl, H2O, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by column chromatograhpy on silica gel with 2:1 hexane:EtOAc afforded 39 (460 mg) as a white foam. 1H NMR (CDCl3, 300 MHz), mixture of rotamers: δ9.96 (d, J=18.9 Hz, 0.5H), 7.68 (d, J=9 Hz, 1H), 7.61 (d, J=7.5 Hz, 1H), 7.39-7.28 (m, 7H), 7.10 (dd, J=7.2, 15 Hz, 1H), 5.32-5.28 (m, 0.5H), 5.20-5.12 (m, 2.5H), 4.81-4.78 (m, 0.5H), 4.70 (d, J=6.6 Hz, 0.5H), 4.55-4.49 (m, 1H), 4.39-4.27 (m, 1.5H), 4.02-3.99 (m, 1H), 3.54-3.40 (m, 2H), 3.22-3.09 (m, 2H), 2.51-2.26 (m, 1H), 2.10-2.09 (m, 0.5H), 1.94-1.62 (m, 8H), 1.52-1.43 (m, 11H), 1.18-0.86 (m, 6H) ppm. Mass spectrum, m/z [605.7] (M+H)+.

Workup

  1. washwashed with H2O, 1M HCl, H2O, saturated aqueous NaHCO3, brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by column chromatograhpy on silica gel with 2:1 hexane

Sources & evidence

ORD record
ord-f671432fd3064f73bbaa767f8db0d5d4
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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