HCID 86669384, compound → HCID 52914693, compound

HRID 537368Notes

Reaction equation

HRID 537368 reaction equation
[OH:1][C:2]1([C:41]2[CH:59]=[CH:58][CH:57]=[CH:56][C:42]=2[CH2:43][CH2:44][O:45][CH2:46][CH2:47][CH2:48][C:49]([O:51]C(C)(C)C)=[O:50])[CH2:7][CH2:6][N:5]([C:8]([C@:10]2([O:31][C:32]3[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[S:34][CH:33]=3)[CH2:15][CH2:14][CH2:13][N:12]([C:16](=[O:27])[C:17]3[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:20]=[CH:19][N:18]=3)[C@@H:11]2[CH2:28][CH2:29][CH3:30])=[O:9])[CH2:4][CH2:3]1>C1(C)C=CC=CC=1>[OH:1][C:2]1([C:41]2[CH:59]=[CH:58][CH:57]=[CH:56][C:42]=2[CH2:43][CH2:44][O:45][CH2:46][CH2:47][CH2:48][C:49]([OH:51])=[O:50])[CH2:3][CH2:4][N:5]([C:8]([C@:10]2([O:31][C:32]3[CH:36]=[C:35]([C:37]([F:40])([F:38])[F:39])[S:34][CH:33]=3)[CH2:15][CH2:14][CH2:13][N:12]([C:16](=[O:27])[C:17]3[C:22]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:20]=[CH:19][N:18]=3)[C@@H:11]2[CH2:28][CH2:29][CH3:30])=[O:9])[CH2:6][CH2:7]1

Participants

3

Reactant 1

HCID 86669384HCID 86669384, compound

Product 1

HCID 52914693HCID 52914693, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Silica gel (230-400 mesh, 88 mg) was added to tert-butyl 4-(2-(4-hydroxy-1-((2R,3S)-2-propyl-1-(3-(trifluoromethyl)picolinoyl)-3-(5-(trifluoromethyl)thiophen-3-yloxy)piperidine-3-carbonyl)piperidin-4-yl)phenethoxy)butanoate (15 mg, 0.018 mmol) in toluene (0.5 mL) and heated to reflux with vigorous stirring for 6 h. Additional silica gel (44 mg) and toluene (0.5 mL) were added and reflux was continued for 18 h. The reaction mixture was cooled to room temperature and the silica gel was removed by filtration through Celite washing with methylene chloride/methanol (1:1, 10 mL) and methanol (10 mL). The solvent was removed under reduced pressure and the residue purified by silica gel chromatography (methanol/methylene chloride) to provide A63 (9.8 mg, 70% yield) as a white solid after lyophilization from water/acetonitrile: 1H NMR (300 MHz, CDCl3) 8.81 (d, J=4.8 Hz, 1H), 8.06 (d, J=8.1 Hz, 1H), 7.49 (dd, J=8.0, 5.0 Hz, 1H), 7.23-7.05 (m, 3H), 6.71 (d, J=7.5 Hz, 1H), 6.68 (d, J=1.8 Hz, 0.7H), 6.54 (d, J=1.8 Hz, 0.3H), 5.57-5.40 (m, 1H), 4.93-4.73 (m, 1H), 4.70-4.45 (m, 2H), 3.95-3.01 (m, 9H), 2.81 (dt, J=14.1, 3.67 Hz, 1H), 2.59-1.24 (m, 18H), 1.08-0.96 (m, 3H).

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. temperaturereflux
  4. waitwas continued for 18 h
  5. customthe silica gel was removed by filtration through Celite
  6. washwashing with methylene chloride/methanol (1:1, 10 mL) and methanol (10 mL)
  7. customThe solvent was removed under reduced pressure
  8. customthe residue purified by silica gel chromatography (methanol/methylene chloride)
  9. customto provide A63 (9.8 mg, 70% yield) as a white solid after lyophilization from water/acetonitrile

Sources & evidence

ORD record
ord-45be7718c65c4c4dac3632e54c3ec99f
Source dataset
uspto-grants-2014_10
Patent number
US08859776B2

Reaction notes

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