Trifluoroacetic acid → HCID 10386445, compound

HRID 853683Notes

Reaction equation

HRID 853683 reaction equation
C([O:14][C:15]1[C:16]2[C:34](=[O:35])[N:33]([CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[CH2:32][C:17]=2[C:18]([C:25]2[C:26]([CH3:31])=[N:27][O:28][C:29]=2[CH3:30])=[C:19]2[C:24]=1[N:23]=[CH:22][CH:21]=[CH:20]2)(C1C=CC=CC=1)C1C=CC=CC=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[CH3:31][C:26]1[C:25]([C:18]2[C:17]3[CH2:32][N:33]([CH2:36][C:37]4[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=4)[C:34](=[O:35])[C:16]=3[C:15]([OH:14])=[C:24]3[C:19]=2[CH:20]=[CH:21][CH:22]=[N:23]3)=[C:29]([CH3:30])[O:28][N:27]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58928724HCID 58928724, compound

Product 1

HCID 10386445HCID 10386445, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 279 dissolved in dichloromethane (1 mL) was added trifluoroacetic acid (100 μl) and triethylsilane (200 μl). The reaction mixture was stirred at room temperature for ½ hours under an inert atmosphere then concentrated in vacuo. The residue was dissolved in DMSO (1 mL) and purified by prep-HPLC to remove Ph3PO. The crude mixture was diluted with EtOAC and extracted with 1N HCl. The aqueous phase containing product 280 was re-purified by HPLC to afford 5-(3,5-dimethyl-isoxazol4-yl)-7-(4-fluoro-benzyl)-9-hydroxy-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one 280, (0.4 mg) as a TFA salt solid: 1H NMR (CD3OD) δ 9.0 (d, 1H), 8.1 (d, 1H), 8.0 (s, 1H), 7.7 (m, 1H), 7.4 (dd, 1H), 7.1 (t, 2H), 4.8 (s, 2H), 4.2(s, 2H), 2.0 (s, s, 2×3H); MS: 404 (M+1). HPLC conditions: mobile phase A was 0.1% TFA in water, mobile phase b was 0.1% TFA in CH3CN; gradient from 5% to 60% B in 20 min; flow rate was 20 mL/min; column was Phenomenex, luna 5μ, C18 (2), 150 mm×21.1 mm.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was dissolved in DMSO (1 mL)
  3. custompurified by prep-HPLC
  4. customto remove Ph3PO
  5. additionThe crude mixture was diluted with EtOAC
  6. extractionextracted with 1N HCl
  7. additionThe aqueous phase containing product 280
  8. customwas re-purified by HPLC

Sources & evidence

ORD record
ord-3158fd9c013c4ca79463299fe9b62120
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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