Water → HCID 71062673, compound

HRID 528934Notes

Reaction equation

HRID 528934 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].ClC(Cl)(Cl)[C:57]([N:59]=C=O)=[O:58].C([O-])([O-])=O.[K+].[K+].O>C(Cl)Cl.CO>[C:57](=[O:58])([O:16][CH2:15][CH2:14][C:11]1[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]=[C:8]([C:6](=[O:7])[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:51][CH2:52][CH2:53][CH3:54])[C:12]=1[Cl:13])[NH2:59]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium Carbonate2×HCID 76400Trichloroacetyl isocyanateHCID 71062175HCID 71062175, compound

Product 1

HCID 71062673HCID 71062673, compoundYield 47.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 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, 20 mg, 0.026 mmol) in CH2Cl2 (0.5 mL) was added trichloroacetyl isocyanate (4 μl, 0.031 mmol). After stirring at 0° C. for 30 min, K2CO3 (2 mg, 0.014 mmol) and MeOH (0.5 mL) were added. The ice bath was removed, and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was then diluted with water and EtOAc. The aqueous layer was extracted with EtOAc (2×), and the combined organic extracts were washed with sat. aq. NaCl solution, dried over Na2SO4, filtered and concentrated in vacuo to afford a colorless oil. The oil was dissolved in MeOH (3.0 mL) and water (3.0 mL) and K2CO3 (120 mg, 0.84 mmol) was added. The reaction mixture was stirred at room temperature for 30 minutes and then partitioned between EtOAc and H2O. The layers were separated, and the aqueous layer was extracted with EtOAc (2×). The combined organic extracts were washed with sat. aq. NaCl solution, dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound (10 mg, 44%) as a white solid. 1H NMR (CD3OD, 1.5:1 mixture of amide rotamers) δ 8.73 (br s, 1H), 8.13-8.04 (m, 4.5H), 8.02-7.95 (m, 2H), 7.78-7.64 (m, 3H), 7.23-7.08 (m, 4H), 7.02-6.88 (m, 0.5H), 4.94-4.89 (m, 1H), 4.67-4.41 (m, 1H), 4.25 (t, J=6.5 Hz, 2H), 4.18-4.05 (m, 1.5H), 4.01-3.71 (m, 1.5H), 3.65-3.46 (m, 4H), 3.37-3.34 (m, 2H), 3.02 (t, J=6.5 Hz, 1.5H), 2.92-2.77 (m, 1.5H), 1.68-1.53 (m, 2H), 1.31-1.25 (m, 3H), 1.20-1.17 (m, 1H), 0.99 (t, J=7.4 Hz, 2H), 0.94-0.86 (m, 3H), 0.78-0.73 (m, 2H), 0.68 (t, J=6.4 Hz, 1H); MS(ESI+) m/z 813.5 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred at room temperature for 3 h
  3. additionThe reaction mixture was then diluted with water and EtOAc
  4. extractionThe aqueous layer was extracted with EtOAc (2×)
  5. washthe combined organic extracts were washed with sat. aq. NaCl solution
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a colorless oil
  10. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  11. custompartitioned between EtOAc and H2O
  12. customThe layers were separated
  13. extractionthe aqueous layer was extracted with EtOAc (2×)
  14. washThe combined organic extracts were washed with sat. aq. NaCl solution
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bf7c9b75014d406c8789246c13b7bc54
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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