Trifluoroacetic acid → HCID 57991902, compound

HRID 2075344Notes

Reaction equation

HRID 2075344 reaction equation
[NH2:1][C@@H:2]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1)[CH2:3][N:4]([C:12]1[S:13][C:14]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]=[CH:22][N:21]=[CH:20]3)=[N:15][N:16]=1)C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:1][C@@H:2]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:35])([F:37])[F:36])=[CH:30][CH:29]=1)[CH2:3][NH:4][C:12]1[S:13][C:14]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]=[CH:22][N:21]=[CH:20]3)=[N:15][N:16]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57991936HCID 57991936, compound

Product 1

HCID 57991902HCID 57991902, compoundYield 7.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl(5-(quinazolin-6-yl)-1,3,4-thiadiazol-2-yl)carbamate was obtained as a semi-pure yellow solid from tert-butyl 5-(quinazolin-6-yl)-1,3,4-thiadiazol-2-ylcarbamate using the procedure described previously. To a stirred mixture of tert-butyl (S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl(5-(quinazolin-6-yl)-1,3,4-thiadiazol-2-yl)carbamate (17 mg, 32 μmol) in DCM (2.0 mL) was added TFA (2.0 mL). The overall mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated and the residue taken up in DCM. The mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL). The separated aqueous layer was extracted with DCM (2×5 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by flash column chromatography (eluting with a gradient of DCM to 10% MeOH in DCM) to provide N—((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(quinazolin-6-yl)-1,3,4-thiadiazol-2-amine as a white solid (1.0 mg, 7% yield). LCMS (M+H) 431.1 calc. for C20H18F3N6S 431.1. 1H NMR (400 MHz, CDCl3): δ ppm 9.43 (d, J=2.74 Hz, 1H) 9.35 (d, J=3.13 Hz, 1H) 8.46 (d, J=8.22 Hz, 1H) 8.19 (s, 1H) 8.09 (d, J=5.87 Hz, 1H) 7.60 (d, J=5.87 Hz, 1H) 7.36 (d, J=6.65 Hz, 2H) 3.66 (d, J=13.89 Hz, 1H) 3.40-3.51 (m, 1H) 2.07 (s, 1H) 1.38-1.79 (m, 2H) 1.26 (s, 2H). 2H obscured.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washThe mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL)
  3. extractionThe separated aqueous layer was extracted with DCM (2×5 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (
  8. washeluting with a gradient of DCM to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-fc7e760162ee4f0ba8f972ff672d86e0
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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