Sodium Hydroxide → HCID 67606700, compound

HRID 1965190Notes

Reaction equation

HRID 1965190 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.[C:51]([O:55][C:56]([N:58]1[CH2:62][CH:61]([O:63][CH2:64][C:65]2[CH:70]=[CH:69][C:68]([F:71])=[CH:67][CH:66]=2)[CH:60]2[N:72]([C:75](=[O:82])[CH:76]([NH2:81])[C:77]([CH3:80])([CH3:79])[CH3:78])[CH2:73][CH2:74][CH:59]12)=[O:57])([CH3:54])([CH3:53])[CH3:52].[OH-].[Na+]>CN1C(=O)CCC1.O>[C:51]([O:55][C:56]([N:58]1[CH2:62][CH:61]([O:63][CH2:64][C:65]2[CH:70]=[CH:69][C:68]([F:71])=[CH:67][CH:66]=2)[CH:60]2[N:72]([C:75](=[O:82])[CH:76]([NH:81][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])[C:77]([CH3:80])([CH3:79])[CH3:78])[CH2:73][CH2:74][CH:59]12)=[O:57])([CH3:54])([CH3:52])[CH3:53]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 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 675062084-(2-Amino-3,3-dimethyl-butyryl)-3-(4-fluoro-benzyloxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

Product 1

HCID 67606700HCID 67606700, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A stirred solution of Cbz-N(Me)Ala-OH (7.85 g, 7.70 mmol), HATU (2.95 g, 7.70 mmol), and DIPEA (1.60 mL, 9.10 mmol) in NMP (20 mL) was cooled to 0° C. and amine 47 (7.02 mmol) in NMP (20 mL) was added. The solution was allowed to warm to ambient temperature. After 13 h, the reaction mixture was cooled to 0° C. and 1N NaOH (10 mL) was added. The reaction mixture was diluted with water and extracted with Et2O. The combined organic extracts were washed successively with water, 1N HCl, 10% H3PO4, water, NaHCO3, water, and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated to afford 4.5 g (96%, 2 steps) of 48 as a white foam which was used without further purification. Mass spectrum, m/z [691.2] (M+Na)+.

Workup

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. extractionextracted with Et2O
  3. washThe combined organic extracts were washed successively with water, 1N HCl, 10% H3PO4, water, NaHCO3, water, and brine
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-30fadb7d5aae494687c8657439fc305e
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

Loading…