Trifluoroacetic acid → HCID 57991866, compound

HRID 2075402Notes

Reaction equation

HRID 2075402 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[N:10]=[CH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][C:15]([C:19]1[S:23][C:22]([CH2:24][CH2:25][C@@H:26]([NH:38]C(=O)OC(C)(C)C)[CH2:27][C:28]3[CH:29]=[N:30][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:32][CH:33]=3)=[N:21][N:20]=1)=[CH:14][CH:13]=2>C(Cl)Cl>[NH3:10].[F:8][C:9]1[N:10]=[CH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][C:15]([C:19]1[S:23][C:22]([CH2:24][CH2:25][C@@H:26]([NH2:38])[CH2:27][C:28]3[CH:29]=[N:30][C:31]([C:34]([F:35])([F:37])[F:36])=[CH:32][CH:33]=3)=[N:21][N:20]=1)=[CH:14][CH:13]=2

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86636677HCID 86636677, compound

Product 2

HCID 222AmmoniaHCID 57991866HCID 57991866, compoundYield 164.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1 mL) was added to a solution of tert-butyl (R)-4-(5-(3-fluoroisoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-1-(6-(trifluoromethyl)pyridin-3-yl)butan-2-ylcarbamate (85 mg, 155 μmol) in DCM (1 mL), and the mixture was stirred at room temperature for 2 hours. The mixture was concentrated under reduced pressure, and the resulting yellow oil was purified by reversed phase HPLC (Shimadsu Valiant, Phenomenex Gemini C18 5 μm 100×30 mm, 5% to 50% H2O/MeCN, 0.1% TFA) to deliver a colorless oil. The oil was dissolved in MeOH, absorbed onto ISOLUTE Si-TsOH(SCX-3) (5 g), and washed with MeOH (50 mL) and then with 2 N NH3 in MeOH (30 mL) providing (2R)-4-(5-(3-fluoroisoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-1-(6-(trifluoromethyl)pyridin-3-yl)butan-2-amine (57 mg, 82%) as a light yellow solid. 1H NMR (300 MHz, CD3OD) δ ppm 1.88-2.16 (m, 2 H), 2.85 (d, J=13.6, 7.6 Hz, 1 H), 3.02 (dd, J=13.6, 5.8 Hz, 1 H), 3.15-3.28 (m, 1 H), 3.34-3.49 (m, 2 H), 7.53 (s, 1 H), 7.76 (d, J=8.0 Hz, 1 H), 7.95 (d, J=8.0 Hz, 1 H), 8.15 (dd, J=8.7, 1.3 Hz, 1 H), 8.23 (d, J=8.7 Hz, 1 H), 8.45 (s, 1 H), 8.63 (s, 1 H), 9.05 (s, 1 H). LCMS (API-ES) m/z: 470.0 (M+Na+).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe resulting yellow oil was purified by reversed phase HPLC (Shimadsu Valiant, Phenomenex Gemini C18 5 μm 100×30 mm, 5% to 50% H2O/MeCN, 0.1% TFA)
  3. dissolutionThe oil was dissolved in MeOH
  4. customabsorbed onto ISOLUTE Si-TsOH(SCX-3) (5 g)
  5. washwashed with MeOH (50 mL)

Sources & evidence

ORD record
ord-0cf18ef14d704a7f853824db51bac81d
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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