Trifluoroacetic acid → HCID 178445830, compound

HRID 1044029Notes

Reaction equation

HRID 1044029 reaction equation
[CH2:1]([C@H:5]1[CH2:10][N:9]([C:11]2[N:12]=[C:13]([C:16]3[C:24]4[C:19](=[N:20][CH:21]=[CH:22][CH:23]=4)[N:18](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:17]=3)[S:14][CH:15]=2)[CH2:8][CH2:7][N:6]1C(OC(C)(C)C)=O)[CH:2]([CH3:4])[CH3:3].C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([C@@H:5]1[NH:6][CH2:7][CH2:8][N:9]([C:11]2[N:12]=[C:13]([C:16]3[C:24]4[C:19](=[N:20][CH:21]=[CH:22][CH:23]=4)[NH:18][N:17]=3)[S:14][CH:15]=2)[CH2:10]1)[CH:2]([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 67212610tert-butyl (2S)-2-isobutyl-4-[2-(1-tritylpyrazolo[5,4-b]pyridin-3-yl)thiazol-4-yl]piperazine-1-carboxylate

Product 1

HCID 178445830HCID 178445830, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (2S)-2-isobutyl-4-[2-(1-tritylpyrazolo[5,4-b]pyridin-3-yl)thiazol-4-yl]piperazine-1-carboxylate (149 mg, 0.2176 mmol) and triethylsilane (101.2 mg, 139.0 μL, 0.8704 mmol) in DCM (2 mL) at 0° C. was added TFA (0.3 mL,). Then ice-bath removed and mixture stirred at room temperature for 1 h. Added more TFA (0.3 mL) and stirred for a further 1 h. Basified with minimal sat. NaHCO3 and extracted with EtOAc. Organics combined, washed with small amount of water, brine, dried (MgSO4), filtered and concentrated in vacuo. Crude product purified by flash chromatography (12 g SiO2, 0 to 6% MeOH (containing 10% ammonium hydroxide)/DCM) to leave product as a pale green solid after freeze-drying (MeCN/H2O) (18.18 mg, 24%); 1H NMR DMSO-d6 δ 0.87-0.86 (br m, 1H), 0.92 (dd, 6H), 1.31-1.20 (m, 2H), 1.85-1.76 (m, 1H), 2.36 (t, 1H), 2.71 (td, 1H), 2.87-2.78 (m, 2H), 3.00 (d, 1H), 3.80 (dd, 2H), 6.30 (s, 1H), 7.37 (dd, 1H), 8.64 (m, 2H); ES+ 343.08.

Workup

  1. customThen ice-bath removed
  2. additionAdded more TFA (0.3 mL)
  3. stirringstirred for a further 1 h
  4. extractionextracted with EtOAc
  5. washwashed with small amount of water, brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customCrude product purified by flash chromatography (12 g SiO2, 0 to 6% MeOH (containing 10% ammonium hydroxide)/DCM)
  10. customto leave product as a pale green solid
  11. dry with materialafter freeze-drying (MeCN/H2O) (18.18 mg, 24%)

Sources & evidence

ORD record
ord-d7ba38f7fa734f2a8aac549faf22e5b5
Source dataset
uspto-grants-2013_10
Patent number
US08563576B2

Reaction notes

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