Trifluoroacetic acid → HCID 117843349, compound

HRID 2209189Notes

Reaction equation

HRID 2209189 reaction equation
[CH:1]1([C:4]([OH:6])=O)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(O)(C(F)(F)F)=O.[N:47]1([C:53]2[CH:54]=[CH:55][C:56]([C:59]3[CH:60]=[C:61]([O:68][C@@H:69]([C@H:71]4[CH2:75][NH:74][C:73](=[O:76])[CH2:72]4)[CH3:70])[C:62]4[S:66][CH:65]=[N:64][C:63]=4[CH:67]=3)=[N:57][CH:58]=2)[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1>CN(C=O)C>[CH:1]1([C:4]([N:50]2[CH2:49][CH2:48][N:47]([C:53]3[CH:54]=[CH:55][C:56]([C:59]4[CH:60]=[C:61]([O:68][C@@H:69]([C@H:71]5[CH2:75][NH:74][C:73](=[O:76])[CH2:72]5)[CH3:70])[C:62]5[S:66][CH:65]=[N:64][C:63]=5[CH:67]=4)=[N:57][CH:58]=3)[CH2:52][CH2:51]2)=[O:6])[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 15655Cyclopropanecarboxylic acidHCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117843721HCID 117843721, compound

Product 1

HCID 117843349HCID 117843349, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Cyclopropanecarboxylic acid (9.6 μL, 0.12 mmol) was dissolved in DMF (0.5 mL) along with iPr2NEt (30 μL, 0.17 mmol). To this mixture was added HATU (46 mg, 0.12 mmol). After 10 min, a mixture of the crude TFA salt of 4.23 (0.06 mmol) and iPr2NEt (50 μL, 0.29 mmol) in DMF (0.5 mL) was added. Additional DMF (2×0.25 mL) was used to ensure complete transfer. After 1.5 h, the reaction mixture was partitioned between EtOAc, water, and sat. aq. NaHCO3. The phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel chromatography (0-25% MeOH in DCM) to afford (R)-4-((R)-1-((5-(5-(4-(cyclopropanecarbonyl)piperazin-1-yl)pyridin-2-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one (4.33).

Workup

  1. additionwas added
  2. waitAfter 1.5 h
  3. customthe reaction mixture was partitioned between EtOAc, water, and sat. aq. NaHCO3
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with EtOAc
  6. dry with materialThe combined organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel chromatography (0-25% MeOH in DCM)

Sources & evidence

ORD record
ord-5d37e6f83466455ebfb1be04aafdd6c2
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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