Diisopropylethylamine → (1-{1-[6-(3,4-Difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

HRID 1965172Notes

Reaction equation

HRID 1965172 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([N:35]([CH3:41])[C@H:36]([C:38]([OH:40])=O)[CH3:37])([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].CCN(C(C)C)C(C)C.[NH2:51][CH:52]([C:78]([CH3:81])([CH3:80])[CH3:79])[C:53]([N:55]1[CH2:59][CH2:58][CH:57]2[N:60]([CH:72]3[CH2:77][CH2:76][O:75][CH2:74][CH2:73]3)[CH2:61][CH:62]([O:63][C:64]3[CH:69]=[CH:68][C:67]([F:70])=[C:66]([F:71])[CH:65]=3)[CH:56]12)=[O:54]>CN1C(=O)CCC1>[CH2:28]([O:27][C:25](=[O:26])[N:35]([CH:36]([C:38](=[O:40])[NH:51][CH:52]([C:53]([N:55]1[CH2:59][CH2:58][CH:57]2[N:60]([CH:72]3[CH2:77][CH2:76][O:75][CH2:74][CH2:73]3)[CH2:61][CH:62]([O:63][C:64]3[CH:69]=[CH:68][C:67]([F:70])=[C:66]([F:71])[CH:65]=3)[CH:56]12)=[O:54])[C:78]([CH3:80])([CH3:79])[CH3:81])[CH3:37])[CH3:41])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

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 675142402-Amino-1-[6-(3,4-difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-3,3-dimethyl-butan-1-one

Product 1

HCID 67608273(1-{1-[6-(3,4-Difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl esterYield 81.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
0 °C

Procedure

HATU (126 mg, 0.33 mmol) and Cbz-N(Me)Ala-OH (79 mg, 0.33 mmol) were dissolved in NMP (0.5 mL) and DIPEA (70 μL, 0.39 mmol) was added. The reaction mixture was cooled to 0° C. and a solution of 26 (125 mg, 0.30 mmol) in NMP (2 mL) was added. The reaction mixture was warmed to ambient temperature. After 12 h, the reaction mixture was quenched with 1N NaOH (0.5 mL) and diluted with water. The product was extracted with 10:1 Et2O/EtOAc, and the combined organic extracts were washed successively with water, saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 160 mg of 27 as a beige-colored foam that was used without further purification. Mass spectrum, m/z [657.2] (M+H)+.

Workup

  1. temperatureThe reaction mixture was warmed to ambient temperature
  2. customthe reaction mixture was quenched with 1N NaOH (0.5 mL)
  3. additiondiluted with water
  4. extractionThe product was extracted with 10:1 Et2O/EtOAc
  5. washthe combined organic extracts were washed successively with water, saturated aqueous NaHCO3, and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-5988792eb2bc43258dcb8cec36d2833b
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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