Trifluoroacetic acid → 2-methyl-1-(6-((4-(piperidin-1-yl)-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)pyridin-2-yl)-5,8,11-trioxa-2-azatetradecan-14-oic acid

HRID 926876Notes

Reaction equation

HRID 926876 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[N:21]=[C:20]([CH2:22][N:23]([CH3:42])[CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][C:35]([O:37]C(C)(C)C)=[O:36])[CH:19]=[CH:18][CH:17]=3)=[O:15])=[C:9]([C:43](=[O:60])[NH:44][C:45]3[CH:49]=[CH:48][N:47]([C:50]4[CH:55]=[CH:54][CH:53]=[C:52]([C:56]([F:59])([F:58])[F:57])[CH:51]=4)[N:46]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O>ClCCl>[CH3:42][N:23]([CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36])[CH2:22][C:20]1[CH:19]=[CH:18][CH:17]=[C:16]([C:14](=[O:15])[NH:13][C:10]2[CH:11]=[CH:12][C:7]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[CH:8][C:9]=2[C:43](=[O:60])[NH:44][C:45]2[CH:49]=[CH:48][N:47]([C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([C:56]([F:57])([F:58])[F:59])[CH:51]=3)[N:46]=2)[N:21]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66588149tert-butyl 3-(2-(2-(2-(((6-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)-phenyl)carbamoyl)pyridin-2-yl)methyl)(methyl)amino)ethoxy)ethoxy)ethoxy)propanoate

Product 1

HCID 665881512-methyl-1-(6-((4-(piperidin-1-yl)-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)pyridin-2-yl)-5,8,11-trioxa-2-azatetradecan-14-oic acidYield 16.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 50-mL round bottom flask, was placed a solution of tert-butyl 3-(2-(2-(2-(((6-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)-phenyl)carbamoyl)pyridin-2-yl)methyl)(methyl)amino)ethoxy)ethoxy)ethoxy)propanoate (210 mg, 0.25 mmol, 1.00 equiv) in dichloromethane (4 mL), and trifluoroacetic acid (2 mL). The resulting solution was stirred for 2 h at room temperature. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The crude product was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 32.9 mg (13%) of a brown solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.81-8.78(d, J=9.3 Hz, 1H), 8.48-8.47(d, J=2.7 Hz, 1H), 8.33-8.31(d, J=7.5 Hz, 1H), 8.21-8.16(d, J=7.5 Hz, 2H), 7.87-7.86(d, J=2.4 Hz, 1H), 7.79-7.72(m, 2H), 7.64-7.62(d, J=6.9 Hz, 2H), 6.98-6.97(d, J=2.4 Hz, 1H), 4.75(s, 2H), 3.80-3.77(t, J=4.5 Hz, 2H), 3.66-3.47(m, 16H), 3.11-3.09(d, J=6.3 Hz, 3H), 2.49-2.45(d, J=6 Hz, 2H), 1.94-1.75(m, 6H). MS (ES, m/z): 782 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe crude product was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-b13f2e5378dd4fd3b117248c37681310
Source dataset
uspto-grants-2016_03
Patent number
US09289430B2

Reaction notes

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