Carbamate → HCID 71073339, compound

HRID 2408934Notes

Reaction equation

HRID 2408934 reaction equation
[C:1](=[O:4])([O-])[NH2:2].Cl.[CH3:6][CH2:7][N:8](C(C)C)C(C)C.[C:15]([O:19][C:20]([NH:22][C@@H:23]([C@@H:27]([CH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1)F)[C:24]([OH:26])=O)=[O:21])([CH3:18])([CH3:17])[CH3:16].CN(C(ON1N=[N:49][C:44]2[CH:45]=[CH:46][CH:47]=NC1=2)=[N+](C)C)C.[F:51][P-](F)(F)(F)(F)F.[C:58]([O-:61])(O)=O.[Na+].[CH3:63][N:64]([CH:66]=O)C>O1CCOCC1.CCOCC>[C:15]([O:19][C:20](=[O:21])[NH:22][CH:23]([C:24](=[O:26])[NH:49][C:44]1([CH:58]([OH:61])[C:1](=[O:4])[NH:2][C:7]2[CH:6]=[CH:66][N:64]([CH3:63])[N:8]=2)[CH2:45][CH2:46][CH2:47]1)[CH2:27][C:29]1([F:51])[CH2:33][CH2:32][CH2:31][CH2:30]1)([CH3:16])([CH3:17])[CH3:18]

Participants

10

Reactant 7

HCID 276CarbamateHCID 313Hydrochloric Acid2×HCID 6228Dimethylformamide2×HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71073451HCID 71073451, compound

Product 1

HCID 71073339HCID 71073339, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

Carbamate 9a was treated with 4M HCl in 1,4-dioxane to remove the Boc protecting group. The afforded bis-HCl salt (220 mg, 0.74 mmol) was dissolved in DMF (2 mL) and DIPEA (260 μL, 1.5 mmol) was added and the mixture was cooled to 0° C. In a separate flask (2R,3R)-2-(tert-butoxycarbonylamino)-3-cyclopentyl-3-fluoropropanoic acid (201 mg, 0.74 mmol, prepared as described in WO06/064286) was dissolved in DMF and DIPEA (385 μL, 2.2 mmol) was added and the mixture was cooled to 0° C. whereafter HATU (295 mg, 0.77 mmol) was added and the reaction was stirred for 5 min. The contents of the second flask were added dropwise to the first flask and the stirring was continued for 1 h. Sat aq NaHCO3 (15 mL) and Et2O (15 mL) were added and the phases were separated. The aqueous phase was extracted with 2×15 mL EtOAc and the combined organic layers were washed with sat aq NaHCO3 (15 mL). The solvent was removed by rotary evaporation and the product was purified by gradient column chromatography (DCM-6% MeOH in DCM). This gave the title compound (332 mg, 93%). ES+ 482.2 [M+H]+.

Workup

  1. customto remove the Boc protecting group
  2. additionwas added
  3. additionThe contents of the second flask were added dropwise to the first flask
  4. waitthe stirring was continued for 1 h
  5. customthe phases were separated
  6. extractionThe aqueous phase was extracted with 2×15 mL EtOAc
  7. washthe combined organic layers were washed with sat aq NaHCO3 (15 mL)
  8. customThe solvent was removed by rotary evaporation
  9. customthe product was purified by gradient column chromatography (DCM-6% MeOH in DCM)

Sources & evidence

ORD record
ord-9ed62be570074066b7af33b682120bdb
Source dataset
uspto-grants-2014_08
Patent number
US08815809B2

Reaction notes

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