HCID 71062175, compound → HCID 71062428, compound

HRID 528932Notes

Reaction equation

HRID 528932 reaction equation
[CH2:1]([N:5]([CH2:51][CH2:52][CH2:53][CH3:54])[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH2:14][CH2:15][OH:16])[N:10]([C:17]2[CH:22]=[CH:21][C:20]([C:23](=[O:38])[NH:24][S:25]([C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=3)(=[O:27])=[O:26])=[CH:19][C:18]=2[C:39]([N:41]2[CH2:50][CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42]2)=[O:40])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].CC(C)=[O:57].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[Cl:13][C:12]1[C:8]([C:6](=[O:7])[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:51][CH2:52][CH2:53][CH3:54])=[N:9][N:10]([C:17]2[CH:22]=[CH:21][C:20]([C:23](=[O:38])[NH:24][S:25]([C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=3)(=[O:27])=[O:26])=[CH:19][C:18]=2[C:39]([N:41]2[CH2:50][CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42]2)=[O:40])[C:11]=1[CH2:14][C:15]([OH:57])=[O:16]

Participants

4

Reactant 2

HCID 71062175HCID 71062175, compoundHCID 131709961Jones' reagent2×

Product 1

HCID 71062428HCID 71062428, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To N,N-dibutyl-4-chloro-5-(2-hydroxyethyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (Example 170, 27 mg, 0.035 mmol) in acetone (640 μL) was added Jones reagent (39 μL, 0.11 mmol). The resulting reaction mixture was stirred at room temperature for 25 min. Additional Jones reagent (39 μL, 0.11 mmol) was added and stirring was continued for 1.5 h. The reaction mixture was then quenched with i-PrOH followed by water. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed with sat. aq. NaCl solution and dried over Na2SO4. After filtering through a pipette containing a small plug of CELITE®, concentration in vacuo afforded a yellow oil. The crude oil was purified by preparative HPLC to give the title compound (6 mg, 22%) as a white solid after lyophilization. 1H NMR (CD3OD, 2:1 mixture of amide rotamers) δ 8.56 (s, 1H), 8.19 (ddd, J=8.4 Hz, 3.2, 1.9 1H), 8.12 (d, J=1.8 Hz, 1H), 8.04-7.99 (m, 2H), 7.96-7.90 (m, 2H), 7.85 (dd, J=12.8, 8.4 Hz, 1H), 7.63-7.54 (m, 2H), 7.25-7.06 (m, 3.5H), 6.94 (d, J=7.0 Hz, 0.5H), 4.77-4.41 (m, 1.5H), 4.09 (br s, 0.5H), 3.79-3.38 (m, 5H), 3.24-2.67 (m, 5H), 1.60-0.84 (m, 11H), 0.78 (t, J=7.3 Hz, 2H), 0.71-0.65 (m, 1H); MS(ESI+) m/z 784.3 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. stirringstirring
  3. waitwas continued for 1.5 h
  4. customThe reaction mixture was then quenched with i-PrOH
  5. extractionThe aqueous layer was extracted with EtOAc (3×)
  6. washthe combined organics were washed with sat. aq. NaCl solution
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtering through a pipette
  9. additioncontaining
  10. concentrationa small plug of CELITE®, concentration in vacuo
  11. customafforded a yellow oil
  12. customThe crude oil was purified by preparative HPLC

Sources & evidence

ORD record
ord-430e61d6e1cf4ea9838561d1843e25d0
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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