Trifluoroacetic acid → HCID 54670944, compound

HRID 869032Notes

Reaction equation

HRID 869032 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9]1[C:10]([C:27]#[C:28][C:29]2[CH:30]=[C:31]([CH:44]=[CH:45][CH:46]=2)[O:32][CH2:33][CH2:34][CH2:35][NH:36]C(=O)OC(C)(C)C)=[N:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])=[CH:17][CH:16]=2)=[CH:13][N:14]=1>C(Cl)Cl>[NH2:36][CH2:35][CH2:34][CH2:33][O:32][C:31]1[CH:30]=[C:29]([C:28]#[C:27][C:10]2[C:9]([NH2:8])=[N:14][CH:13]=[C:12]([C:15]3[CH:16]=[CH:17][C:18]([S:21]([CH:24]([CH3:25])[CH3:26])(=[O:23])=[O:22])=[CH:19][CH:20]=3)[N:11]=2)[CH:46]=[CH:45][CH:44]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68103793HCID 68103793, compound

Product 1

HCID 54670944HCID 54670944, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1 mL) was added to a stirred solution of tert-Butyl (3-(3-((3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)ethynyl)phenoxy)propyl)carbamate (crude residue used directly from Step 1) in DCM (5 mL) at ambient temperature. The reaction was allowed to stir at this temperature for 6 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The reaction mixture was passed through a 5 g SCX-2 cartridge and washed with MeOH. The product was eluted by washing the cartridge with 2M NH3 in MeOH. The solvent was removed in vacuo and the residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the mono-TFA salt of the title compound as a yellow solid (24 mg, 37% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.18 (d, 6H), 2.00-2.06 (m, 2H), 2.97-3.02 (m, 2H), 3.46 (sept, 1H), 4.13 (t, 2H), 7.05-7.08 (m, 1H), 7.17 (s, 2H), 7.39-7.41 (m, 3H), 7.71 (s, 3H), 7.91 (d, 2H), 8.23 (d, 2H) and 8.77 (s, 1H) ppm; MS (ES+) 451.2.

Workup

  1. customat ambient temperature
  2. customThe solvent was removed in vacuo
  3. customthe residue azeotroped with DCM (×2) and ether (×2)
  4. washwashed with MeOH
  5. washThe product was eluted
  6. washby washing the cartridge with 2M NH3 in MeOH
  7. customThe solvent was removed in vacuo
  8. customthe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-c5ed642a7bc24f14a765116d4bf9005b
Source dataset
uspto-grants-2015_03
Patent number
US08969356B2

Reaction notes

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