Dicyclohexylamine → 4-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

HRID 1965168Notes

Reaction equation

HRID 1965168 reaction equation
[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([OH:9])=O)[C:3]([CH3:6])([CH3:5])[CH3:4].C1CCC(NC2CCCCC2)CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[C:64]([O:68][C:69]([N:71]1[CH2:75][CH:74]([O:76][C:77]2[CH:82]=[CH:81][C:80]([F:83])=[C:79]([F:84])[CH:78]=2)[CH:73]2[NH:85][CH2:86][CH2:87][CH:72]12)=[O:70])([CH3:67])([CH3:66])[CH3:65]>CN1C(=O)CCC1.CCOC(C)=O.CCOCC>[C:64]([O:68][C:69]([N:71]1[CH2:75][CH:74]([O:76][C:77]2[CH:82]=[CH:81][C:80]([F:83])=[C:79]([F:84])[CH:78]=2)[CH:73]2[N:85]([C:7](=[O:9])[CH:2]([NH:1][C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[C:3]([CH3:4])([CH3:5])[CH3:6])[CH2:86][CH2:87][CH:72]12)=[O:70])([CH3:67])([CH3:65])[CH3:66]

Participants

9

Reactant 5

HCID 7582DicyclohexylamineHCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9899995(2S)-2-(((benzyloxy)carbonyl)amino)-3,3-dimethylbutanoic acidHCID 676064563-(3,4-Difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

Product 1

HCID 676074394-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a solution containing Cbz-Tle-OH.DCHA salt (4.1 g, 9.0 mmol) and HATU (3.8 g, 10 mmol) in NMP (50 mL) was added NMM (1.5 mL), followed by a solution of crude 22 (2.6 g, 7.5 mmol) in NMP (50 mL) at room temperature. The reaction mixture was stirred at room temperature. After 16 h, the reaction mixture was diluted with 10% EtOAc in Et2O, washed successively with water, 1N HCl, 1N NaOH, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude residue was purified by RP-HPLC (2″ Dynamax® C18; 10-100% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford 3.5 g of 23 as white foam. Mass spectrum, m/z [688.3] (M+H)+.

Workup

  1. washwashed successively with water, 1N HCl, 1N NaOH, and brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by RP-HPLC (2″ Dynamax® C18
  6. wait10-100% ACN/water containing 0.1% HOAc over 30 min

Sources & evidence

ORD record
ord-33c5dd7a1f61474b9e8d7757c3a9f7a5
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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