Diisopropylethylamine → HCID 53476561, compound

HRID 245219Notes

Reaction equation

HRID 245219 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[CH2:19]([O:21][C:22]1[CH:31]=[C:30]2[C:25]([C:26]([C:55](O)=[O:56])=[C:27]([CH2:42][N:43]3[CH2:48][CH2:47][CH:46]([N:49]4[CH2:54][CH2:53][O:52][CH2:51][CH2:50]4)[CH2:45][CH2:44]3)[C:28]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=3)=[N:29]2)=[CH:24][C:23]=1[S:58]([CH2:61][CH3:62])(=[O:60])=[O:59])[CH3:20].[F:63][C:64]([F:74])([F:73])[C@@H:65]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)[NH2:66].C(N(CC)C(C)C)(C)C>C(OCC)(=O)C.ClCCl.C([O-])(O)=O.[Na+]>[CH2:19]([O:21][C:22]1[CH:31]=[C:30]2[C:25]([C:26]([C:55]([NH:66][C@H:65]([C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=3)[C:64]([F:63])([F:73])[F:74])=[O:56])=[C:27]([CH2:42][N:43]3[CH2:44][CH2:45][CH:46]([N:49]4[CH2:50][CH2:51][O:52][CH2:53][CH2:54]4)[CH2:47][CH2:48]3)[C:28]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:40])([F:41])[F:39])[CH:33]=3)=[N:29]2)=[CH:24][C:23]=1[S:58]([CH2:61][CH3:62])(=[O:59])=[O:60])[CH3:20]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydride2×HCID 11789718(alphaR)-alpha-(Trifluoromethyl)benzenemethanamineHCID 67418827HCID 67418827, compound

Product 1

HCID 53476561HCID 53476561, compoundYield 66.1%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

T3P (2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide, 0.262 mL of a 50% solution in ethyl acetate, 0.440 mmol) was added to a solution of 7-(ethyloxy)-6-(ethylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.200 g, 0.315 mmol), (1R)-2,2,2-trifluoro-1-phenylethanamine (0.087 g, 0.409 mmol), N,N-diisopropylethylamine (10.99 μL, 0.063 mmol) in dichloromethane (4 mL) at 0° C. The mixture was stirred at 0° C. for 2 h, warmed to room temperature, and stirred overnight. The solution was diluted with saturated aqueous NaHCO3 and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in DMSO and purified via HPLC (Waters, Sunfire, 30×75 mm column, 50 mL/min, 20-60% MeCN/H2O with 0.1% TFA). The fractions containing the product were neutralized with saturated aqueous NaHCO3 and extracted with methylene chloride (three times). The combined organic extracts were washed with brine (two times), dried over Na2SO4, filtered, and concentrated in vacuo to afford 7-(ethyloxy)-6-(ethylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.165 g, 63% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ9.75 (br. s., 1H), 8.77 (s, 1H), 7.81 (s, 1H), 7.74-7.79 (m, 1H), 7.62-7.70 (m, 2H), 7.52-7.59 (m, 3H), 7.40-7.50 (m, 3H), 6.25 (br. s., 1H), 4.29-4.39 (m, 2H), 3.64-3.71 (m, 4H), 3.53-3.64 (m, 2H), 3.48 (q, J=7.03 Hz, 2H), 2.63 (br. s., 1H), 2.37-2.46 (m, 4H), 2.22 (br. s., 1H), 1.97-2.09 (m, 1H), 1.67 (br. s., 4H), 1.58 (t, J=6.90 Hz, 3H), 1.50 (br. s., 1H), 1.31 (t, J=7.40 Hz, 3H), 1.08-1.24 (m, 1H); MS (m/z) 793.2 (M+H+).

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred overnight
  3. extractionextracted with methylene chloride (three times)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in DMSO
  9. custompurified via HPLC (Waters, Sunfire, 30×75 mm column, 50 mL/min, 20-60% MeCN/H2O with 0.1% TFA)
  10. additionThe fractions containing the product
  11. extractionextracted with methylene chloride (three times)
  12. washThe combined organic extracts were washed with brine (two times)
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5449fedeaf1840baac2ce7e72795fb68
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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