Trifluoroacetic acid → 1-(4-(2-Amino-4-methylthiazol-5-yl)pyridin-2-yl)cyclobutanecarbonitrile

HRID 2370371Notes

Reaction equation

HRID 2370371 reaction equation
C(OC(=O)[NH:7][C:8]1[S:9][C:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([C:20]3([C:24]#[N:25])[CH2:23][CH2:22][CH2:21]3)[CH:15]=2)=[C:11]([CH3:13])[N:12]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1[S:9][C:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([C:20]3([C:24]#[N:25])[CH2:23][CH2:22][CH2:21]3)[CH:15]=2)=[C:11]([CH3:13])[N:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59293719{5-[2-(1-Cyano-cyclobutyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-carbamic acid tert-butyl ester

Product 1

HCID 592937411-(4-(2-Amino-4-methylthiazol-5-yl)pyridin-2-yl)cyclobutanecarbonitrileYield 82.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of {5-[2-(1-cyano-cyclobutyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-carbamic acid tert-butyl ester (Step 19.2) (300 mg), DCM (5 mL) and TFA (1 mL) is stirred for 4 h at rt, quenched by addition of a saturated solution of NaHCO3 (50 mL), and extracted with DCM (3×75 mL). The organic phase is washed with a saturated solution of NaHCO3 (2×50 mL), dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel column chromatography (DCM/MeOH, 1:0→96:4) to afford 181 mg of the title compound as a yellow solid: ESI-MS: 271.1 [M+H]+; tR=2.48 min (System 1); TLC: Rf=0.45 (DCM/MeOH, 9:1).

Workup

  1. customquenched by addition of a saturated solution of NaHCO3 (50 mL)
  2. extractionextracted with DCM (3×75 mL)
  3. washThe organic phase is washed with a saturated solution of NaHCO3 (2×50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel column chromatography (DCM/MeOH, 1:0→96:4)

Sources & evidence

ORD record
ord-9e1627bd0e0a4a6d8f53dd9b980aca48
Source dataset
uspto-grants-2014_04
Patent number
US08710085B2

Reaction notes

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