Hydrochloric Acid → N-(1-cyanocyclopropyl)-3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]propionamide

HRID 1696061Notes

Reaction equation

HRID 1696061 reaction equation
[N:1]1([S:7]([CH2:10][C@H:11]([NH:15][C@@H:16]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[C:17]([F:20])([F:19])[F:18])[C:12]([OH:14])=O)(=[O:9])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.[NH2:29][C:30]1([C:33]#[N:34])[CH2:32][CH2:31]1.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>CN(C=O)C.CCOC(C)=O>[C:33]([C:30]1([NH:29][C:12](=[O:14])[C@@H:11]([NH:15][C@@H:16]([C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[C:17]([F:18])([F:20])[F:19])[CH2:10][S:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)(=[O:9])=[O:8])[CH2:32][CH2:31]1)#[N:34]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 5568881-AminocyclopropanecarbonitrileHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672773213-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]-propionic acid

Product 1

HCID 11576559N-(1-cyanocyclopropyl)-3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]propionamideYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]-propionic acid (0.034 g, 0.082 mmol) and the HCl salt of 1-aminocyclopropane-carbonitrile (OmegaChem, 0.013 g, 0.107 mmol) in DMF (1 mL) at rt was added solid HATU (PacificChem, 0.041 g, 0.107 mmol) in one portion followed by DIPEA (Aldrich, 0.043 mL, 0.246 mmol) to produce a bright yellow, clear solution. After stirring at rt for 1 h, the reaction was diluted in EtOAc and quenched with 10% aqueous NaHCO3. Water was added to dissolve precipitated solids. The aqueous layer was separated and extracted with EtOAc. The combined organics were washed with brine and dried over anhydrous Na2SO4. Following concentration in vacuo, the crude product was purified by column chromatography on SiO2 (2/1 EtOAc/Hex). Following concentration in vacuo, 0.020 g (51%) of N-(1-cyanocyclopropyl)-3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]propionamide was obtained as a white foamy solid with repeated concentration from CH2Cl2. LC/MS: 501.4 (M+Na)+; 479.3 (M+H)+; 477.2 (M−H)−.

Workup

  1. customto produce a bright yellow, clear solution
  2. customquenched with 10% aqueous NaHCO3
  3. additionWater was added
  4. dissolutionto dissolve
  5. customprecipitated solids
  6. customThe aqueous layer was separated
  7. extractionextracted with EtOAc
  8. washThe combined organics were washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. concentrationconcentration in vacuo
  11. customthe crude product was purified by column chromatography on SiO2 (2/1 EtOAc/Hex)
  12. concentrationconcentration in vacuo

Sources & evidence

ORD record
ord-a0792e3911a64880860eec742cd44631
Source dataset
uspto-grants-2012_04
Patent number
US08163735B2

Reaction notes

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