Trifluoroacetic acid → HCID 67190512, compound

HRID 546085Notes

Reaction equation

HRID 546085 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]#[C:10][CH2:11][N:12]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:37])[C@@H:19]([C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[C:28]([Cl:36])[CH:27]=2)[CH2:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[N:13]1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl.C(OCC)(=O)C>[NH2:7][CH2:8][C:9]#[C:10][CH2:11][N:12]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:37])[C@@H:19]([C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:33])=[O:34])=[C:28]([Cl:36])[CH:27]=2)[CH2:20][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25]2)=[N:13]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67189016HCID 67189016, compound

Product 1

HCID 67190512HCID 67190512, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-but-2-ynyl)-carbamic acid tert-butyl ester (240 mg, 0.43 mmol) was dissolved in methylene chloride (10 mL) and trifluoroacetic acid (2 mL) was added while stirring. The reaction continued to stir for 45 min. The reaction was concentrated in vacuo at 0° C. to give a yellow oil. The reaction was diluted with ethyl acetate (200 mL), washed with saturated aqueous sodium bicarbonate (2×50 mL), saturated aqueous brine solution (50 mL), dried over magnesium sulfate and concentrated in vacuo to give a yellow oil. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% methanol/ethyl acetate to 10% methanol/ethyl acetate) afforded N-[1-(4-amino-but-2-ynyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (128 mg, 69%) as a thick, faintly yellow oil: ESI-LRMS m/e calcd for C22H27ClN4O3S [M+] 462.2, found 463.2 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03-1.21 (m, 2H, CH2), 1.38-1.82 (m, 8H, 4×CH2), 1.98 (brs, 2H, NH2), 2.05-2.24 (m, 1H, CH), 3.29 (t, J=2.0 Hz, 2H, NCH2), 3.33 (s, 3H, SO2CH3), 3.86-3.95 (m, 1H, CH), 4.87 (t, J=2.0 Hz, 2H, NCH2), 6.44 (d, Jo=2.3 Hz, 1H, Ar), 7.58 (dd, Jo=8.2, Jm=1.6 Hz. 1H, Ar), 7.62 (d, Jo=2.3 Hz, 1H, Ar), 7.68 (d, Jm=1.6 Hz, 1H, Ar), 7.99 (d, Jo=8.2 Hz, 1H, Ar), 10.81 (s, 1H, NH).

Workup

  1. stirringto stir for 45 min
  2. concentrationThe reaction was concentrated in vacuo at 0° C.
  3. customto give a yellow oil
  4. washwashed with saturated aqueous sodium bicarbonate (2×50 mL), saturated aqueous brine solution (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a yellow oil
  8. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% methanol/ethyl acetate to 10% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-8363da3936784b5d921d24c8ca61b433
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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