Diisopropylethylamine → HCID 90646439, compound

HRID 2200032Notes

Reaction equation

HRID 2200032 reaction equation
ClC(Cl)(Cl)C[O:4][C:5](=[O:17])[NH:6][C:7]1[N:8]([CH3:16])[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[Cl:20][C:21]1[CH:26]=[C:25]([CH2:27][N:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)[CH:24]=[C:23]([Cl:35])[C:22]=1[C:36]1[N:40]2[CH:41]=[C:42]([O:45][C@H:46]3[C:55]4[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=4)[C@@H:49]([NH2:56])[CH2:48][CH2:47]3)[CH:43]=[CH:44][C:39]2=[N:38][N:37]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH:5]([OH:17])=[O:4].[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:56][C@@H:49]2[C:50]3[C:55](=[CH:54][CH:53]=[CH:52][CH:51]=3)[C@H:46]([O:45][C:42]3[CH:43]=[CH:44][C:39]4[N:40]([C:36]([C:22]5[C:21]([Cl:20])=[CH:26][C:25]([CH2:27][N:28]6[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]6)=[CH:24][C:23]=5[Cl:35])=[N:37][N:38]=4)[CH:41]=3)[CH2:47][CH2:48]2)=[O:17])[N:8]([CH3:16])[N:9]=1)([CH3:13])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 594208722,2,2-Trichloroethyl (3-tert-butyl-1-methyl-1H-pyrazol-5-yl)carbamate2×HCID 117729017HCID 117729017, compound

Product 1

HCID 90646439HCID 90646439, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
70 °C

Procedure

(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (US 2004/0192653, which is incorporated herein by reference in its entirety; 17 mg, 0.051 mmol) was treated with a solution of Intermediate 13e (25 mg, 0.047 mmol) in 1,4-dioxane (0.4 mL) then DIPEA (10 μL, 0.058 mmol) was added. The mixture was stirred at 70° C. overnight. The mixture was treated with another portion of (5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (7.8 mg, 0.024 mmol) in 1,4-dioxane (0.1 mL) and stirred at 70° C. for 6 h. The mixture was evaporated in vacuo and the residue was partitioned between DCM and water. The aqueous layer was then extracted with DCM (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by HPLC in 4 portions (Method 6, 5-95% MeCN in H2O, 0.1% HCO2H over 30 min), and the isolated product triturated (diethyl ether) to give a solid. The solid was collected by filtration, washed with ether and dried at 50° C. in vacuo to give the title compound. (5.4 mg, 16%). LCMS (Method 5): Rt 3.27 min, m/z 716.3 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.20 (9H, s), 1.82-1.99 (2H, m), 1.99-2.05 (1H, m), 2.05-2.14 (1H, m), 2.18 (3H, s), 2.29-2.42 (4H, br s), 2.42-2.52 (4H, br s, partially obscured by DMSO), 3.56 (3H, s, partially obscured by water), 3.60 (2H, s, partially obscured by water), 4.79-4.88 (1H, m), 5.54 (1H, t, J=4.3 Hz), 6.01 (1H, s), 6.91 (1H, d, J=8.4 Hz), 7.23-7.30 (1H, m), 7.33-7.39 (4H, m), 7.66 (2H, s), 7.91 (1H, d, J=10.2 Hz), 7.97 (1H, d, J=1.7 Hz), 8.21 (1H, s), 8.29 (1H, s).

Workup

  1. stirringstirred at 70° C. for 6 h
  2. customThe mixture was evaporated in vacuo
  3. customthe residue was partitioned between DCM and water
  4. extractionThe aqueous layer was then extracted with DCM (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by HPLC in 4 portions (Method 6, 5-95% MeCN in H2O, 0.1% HCO2H over 30 min)
  10. customthe isolated product triturated (diethyl ether)
  11. customto give a solid
  12. filtrationThe solid was collected by filtration
  13. washwashed with ether
  14. customdried at 50° C. in vacuo

Sources & evidence

ORD record
ord-9832ab61cc754cfd985d03b94440d7da
Source dataset
uspto-grants-2016_06
Patent number
US09359354B2

Reaction notes

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