Lithium Hydroxide → HCID 131733523, compound

HRID 2283433Notes

Reaction equation

HRID 2283433 reaction equation
C([O:3][C:4](=O)[CH:5]([CH3:27])[CH2:6][NH:7][C@@H:8]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([C:18]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)=[O:19])[C:12]=1[F:26])[CH2:9][CH3:10])C.[OH-].[Li+].[Cl-].[NH4+].C([N:36](C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.O.CN(C=O)C>[ClH:17].[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C@H:8]([NH:7][CH2:6][CH:5]([CH3:27])[C:4]([NH2:36])=[O:3])[CH2:9][CH3:10])=[C:12]([F:26])[C:13]=1[C:18]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)=[O:19]

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89544778HCID 89544778, compound

Product 1

HCID 131733523HCID 131733523, compoundYield 17.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 3-{(R)-1-[4-Chloro-2-fluoro-3-(pyridine-3-carbonyl)-phenyl]-propylamino}-2-methyl-propionic acid ethyl ester (0.22 g, 0.54 mmol) in THF: water [4:1] 95 ml) added lithium hydroxide (0.032 g, 1.35 mmol) stirred at ambient for 48 hours, evaporated to dryness, MS: [M+H] 379. To the crude reaction mixture was added DMF(6 ml), ammonium chloride (0.145 g, 2.65 mmol), diisopropylethylamine (1.13 ml, 6.47 mmol) and HATU (0.309, 0.8 mmol) stirred at ambient for 16 hours. Reaction diluted with water and extracted with EtOAc, The organic phase was separated and dried (Na2SO4), filtered and concentrated, purified by Prep HPLC to give the (R,R) product (0.02 g).

Workup

  1. customevaporated to dryness, MS
  2. customTo the crude reaction mixture
  3. stirringstirred at ambient for 16 hours
  4. customReaction
  5. extractionextracted with EtOAc
  6. customThe organic phase was separated
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by Prep HPLC

Sources & evidence

ORD record
ord-ab655aa0fb44458fa8fb4a8c8f1a25db
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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