Trifluoroacetic acid → HCID 59828900, compound

HRID 1191093Notes

Reaction equation

HRID 1191093 reaction equation
[CH2:1]1[CH2:3][CH:2]1[C:4]([NH:6][C:7]1[S:8][CH:9]=[C:10]([C:12]2[CH:26]=[CH:25][C:15]([CH2:16][NH:17]C(OC(C)(C)C)=O)=[CH:14][CH:13]=2)[N:11]=1)=[O:5].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]1[CH2:3][CH:2]1[C:4]([NH:6][C:7]1[S:8][CH:9]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]([CH2:16][NH2:17])=[CH:25][CH:26]=2)[N:11]=1)=[O:5]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59828821HCID 59828821, compound

Product 1

HCID 59828900HCID 59828900, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[(2-cyclopropanecarbonyl-amino)-thiazol-4-yl]-N-(tert-butoxycarbonyl)-benzylamine (2.381 g, 6.376 mmol) in anhydrous DCM (53 mL), add trifluoroacetic acid (45 mL) at room temperature and stir overnight. Concentrate the reaction mixture in vacuo and elute the residue through a SCX column (20 g). Dissolve the residue in DCM, add silica gel (14 g) and concentrate to a powder. Load the powder on to a dry column attached to an Analogix® column (150 g) and purify by preparative liquid chromatography (0:1 to 1:4 2M ammonia in methanol/DCM over 33 min, 1:4 2M ammonia in methanol/DCM over 33 min; 35 mL/min) to afford the title compound (1.668 g, 96%) as an off-white solid. MS (ES+) m/z: 274.1 (M+H)+.

Workup

  1. concentrationConcentrate the reaction mixture in vacuo
  2. washelute the residue through a SCX column (20 g)
  3. dissolutionDissolve the residue in DCM
  4. additionadd silica gel (14 g)
  5. concentrationconcentrate to a powder
  6. custompurify by preparative liquid chromatography (0:1 to 1:4 2M ammonia in methanol/DCM over 33 min, 1:4 2M ammonia in methanol/DCM over 33 min; 35 mL/min)

Sources & evidence

ORD record
ord-656030784cd348779b7f77dc4690bf95
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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