Trifluoroacetic acid → HCID 69631796, compound

HRID 1408107Notes

Reaction equation

HRID 1408107 reaction equation
[F:1][C:2]([F:62])([F:61])[C:3]1[CH:4]=[C:5]([CH:58]=[CH:59][CH:60]=1)[CH2:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:19]=[CH:18][C:17]=2[NH:28][C:29]([C:31]2[N:36]=[C:35]([CH2:37][N:38]([CH3:57])[CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][C:50]([O:52]C(C)(C)C)=[O:51])[CH:34]=[CH:33][CH:32]=2)=[O:30])[CH:11]=1)=[O:9].FC(F)(F)C(O)=O>ClCCl>[F:61][C:2]([F:1])([F:62])[C:3]1[CH:4]=[C:5]([CH:58]=[CH:59][CH:60]=1)[CH2:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:19]=[CH:18][C:17]=2[NH:28][C:29]([C:31]2[N:36]=[C:35]([CH2:37][N:38]([CH3:57])[CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][C:50]([OH:52])=[O:51])[CH:34]=[CH:33][CH:32]=2)=[O:30])[CH:11]=1)=[O:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66586813HCID 66586813, compound

Product 1

HCID 69631796HCID 69631796, compoundYield 45.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL vial, was placed a solution of tert-butyl 3-(2-(2-(2-(((6-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)pyridin-2-yl)methyl)(methyl)amino)ethoxy)ethoxy)ethoxy)-propanoate (200 mg, 0.23 mmol, 1.00 equiv) in dichloromethane (10 mL), and 2,2,2-trifluoroacetic acid (2 mL). The resulting solution was stirred for 3 h at 25° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The residue was dissolved in 50 mL of ethyl acetate. The resulting mixture was washed with 4×30 mL of brine, dried over sodium sulfate, and concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 84.9 mg (31%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.34 (s, 1H), 9.89 (s, 1H), 9.54 (m, 1H), 9.02 (m, 1H), 8.19 (m, 4H), 7.84 (m, 2H), 7.57 (m, 5H), 7.29 (s, 1H), 4.60 (t, J=5.7 Hz, 6H), 3.77 (t, J=4.8 Hz, 2H), 3.48 (m, 16H), 2.84 (s, 3H), 2.51 (m, 2H), 1.9 (s, 4H), 1.7 (s, 2H). MS (ES, m/z): 807 [M+H]+.

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. dissolutionThe residue was dissolved in 50 mL of ethyl acetate
  3. washThe resulting mixture was washed with 4×30 mL of brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (200 mg) was purified by reverse phase HPLC
  7. washeluting with a water/CH3CN gradient
  8. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-63b20a5528224b37a8211a0b9de2671e
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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